A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
Agents that inhibit PROTEIN KINASES.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A species of ciliate protozoa. It is used in biomedical research.
The rate dynamics in chemical or physical systems.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Established cell cultures that have the potential to propagate indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Specific enzyme subunits that form the active sites of the type I and type II cyclic-AMP protein kinases. Each molecule of enzyme contains two catalytic subunits.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)-L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
An aspect of protein kinase (EC in which serine residues in protamines and histones are phosphorylated in the presence of ATP.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
Toluenes in which one hydrogen of the methyl group is substituted by an amino group. Permitted are any substituents on the benzene ring or the amino group.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Proteins prepared by recombinant DNA technology.
A cyclic GMP-dependent protein kinase subtype that is expressed predominantly in INTESTINES, BRAIN, and KIDNEY. The protein is myristoylated on its N-terminus which may play a role its membrane localization.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A monomeric calcium-calmodulin-dependent protein kinase subtype that is primarily expressed in neuronal tissues; T-LYMPHOCYTES and TESTIS. The activity of this enzyme is regulated by its phosphorylation by CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Transport proteins that carry specific substances in the blood or across cell membranes.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Elements of limited time intervals, contributing to particular results or situations.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the association of a p110gamma catalytic subunit and one of the three regulatory subunits of 84, 87, and 101 kDa in size. This subclass of enzymes is a downstream target of G PROTEIN-COUPLED RECEPTORS.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A group of compounds that contain the structure SO2NH2.
The sum of the weight of all the atoms in a molecule.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a serine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and serine and 2 moles of fatty acids.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
A cell line derived from cultured tumor cells.
RNA consisting of two strands as opposed to the more prevalent single-stranded RNA. Most of the double-stranded segments are formed from transcription of DNA by intramolecular base-pairing of inverted complementary sequences separated by a single-stranded loop. Some double-stranded segments of RNA are normal in all organisms.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
The process of moving proteins from one cellular compartment (including extracellular) to another by various sorting and transport mechanisms such as gated transport, protein translocation, and vesicular transport.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
A phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)
A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
A homologous family of regulatory enzymes that are structurally related to the protein silent mating type information regulator 2 (Sir2) found in Saccharomyces cerevisiae. Sirtuins contain a central catalytic core region which binds NAD. Several of the sirtuins utilize NAD to deacetylate proteins such as HISTONES and are categorized as GROUP III HISTONE DEACETYLASES. Several other sirtuin members utilize NAD to transfer ADP-RIBOSE to proteins and are categorized as MONO ADP-RIBOSE TRANSFERASES, while a third group of sirtuins appears to have both deacetylase and ADP ribose transferase activities.
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
A phosphatidylinositol 3-kinase subclass that includes enzymes with a specificity for 1-phosphatidylinositol, 1-phosphatidylinositol 4-phosphate, and 1-phosphatidylinositol 4,5-bisphosphate. Members of this enzyme subclass are activated by cell surface receptors and occur as heterodimers of enzymatic and regulatory subunits.
A chelating agent relatively more specific for calcium and less toxic than EDETIC ACID.
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
A sirtuin family member found primarily in the CELL NUCLEUS. It is an NAD-dependent deacetylase with specificity towards HISTONES and a variety of proteins involved in gene regulation.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
The nonstriated involuntary muscle tissue of blood vessels.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A group of phenyl benzopyrans named for having structures like FLAVONES.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.
A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
The phosphoric acid ester of serine.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.
The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
A phosphatidylinositol 3-kinase subclass that includes enzymes formed through the heterodimerization of a p110 catalytic and a p85, p55, or p50 regulatory subunit. This subclass of enzymes is a downstream target of TYROSINE KINASE RECEPTORS and G PROTEIN-COUPLED RECEPTORS.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.

Intracellular signalling: PDK1--a kinase at the hub of things. (1/431)

Phosphoinositide-dependent kinase 1 (PDK1) is at the hub of many signalling pathways, activating PKB and PKC isoenzymes, as well as p70 S6 kinase and perhaps PKA. PDK1 action is determined by colocalization with substrate and by target site availability, features that may enable it to operate in both resting and stimulated cells.  (+info)

Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast. (2/431)

BACKGROUND: In animal cells, recruitment of phosphatidylinositol 3-kinase by growth factor receptors generates 3-phosphoinositides, which stimulate 3-phosphoinositide-dependent protein kinase-1 (PDK1). Activated PDK1 then phosphorylates and activates downstream protein kinases, including protein kinase B (PKB)/c-Akt, p70 S6 kinase, PKC isoforms, and serum- and glucocorticoid-inducible kinase (SGK), thereby eliciting physiological responses. RESULTS: We found that two previously uncharacterised genes of Saccharomyces cerevisiae, which we term PKH1 and PKH2, encode protein kinases with catalytic domains closely resembling those of human and Drosophila PDK1. Both Pkh1 and Pkh2 were essential for cell viability. Expression of human PDK1 in otherwise inviable pkh1Delta pkh2Delta cells permitted growth. In addition, the yeast YPK1 and YKR2 genes were found to encode protein kinases each with a catalytic domain closely resembling that of SGK; both Ypk1 and Ykr2 were also essential for viability. Otherwise inviable ypk1Delta ykr2Delta cells were fully rescued by expression of rat SGK, but not mouse PKB or rat p70 S6 kinase. Purified Pkh1 activated mammalian SGK and PKBalpha in vitro by phosphorylating the same residue as PDK1. Pkh1 activated purified Ypk1 by phosphorylating the equivalent residue (Thr504) and was required for maximal Ypk1 phosphorylation in vivo. Unlike PKB, activation of Ypk1 and SGK by Pkh1 did not require phosphatidylinositol 3,4,5-trisphosphate, consistent with the absence of pleckstrin homology domains in these proteins. The phosphorylation consensus sequence for Ypk1 was similar to that for PKBalpha and SGK. CONCLUSIONS: Pkh1 and Pkh2 function similarly to PDK1, and Ypk1 and Ykr2 to SGK. As in animal cells, these two groups of yeast kinases constitute two tiers of a signalling cascade required for yeast cell growth.  (+info)

Primary structure, tissue distribution, and expression of mouse phosphoinositide-dependent protein kinase-1, a protein kinase that phosphorylates and activates protein kinase Czeta. (3/431)

Phosphoinositide-dependent protein kinase-1 (PDK1) is a recently identified serine/threonine kinase that phosphorylates and activates Akt and p70(S6K), two downstream kinases of phosphatidylinositol 3-kinase. To further study the potential role of PDK1, we have screened a mouse liver cDNA library and identified a cDNA encoding the enzyme. The predicted mouse PDK1 (mPDK1) protein contained 559 amino acids and a COOH-terminal pleckstrin homology domain. A 7-kilobase mPDK1 mRNA was broadly expressed in mouse tissues and in embryonic cells. In the testis, a high level expression of a tissue-specific 2-kilobase transcript was also detected. Anti-mPDK1 antibody recognized multiple proteins in mouse tissues with molecular masses ranging from 60 to 180 kDa. mPDK1 phosphorylated the conserved threonine residue (Thr402) in the activation loop of protein kinase C-zeta and activated the enzyme in vitro and in cells. Our findings suggest that there may be different isoforms of mPDK1 and that the protein is an upstream kinase that activates divergent pathways downstream of phosphatidylinositol 3-kinase.  (+info)

p70 S6 kinase is regulated by protein kinase Czeta and participates in a phosphoinositide 3-kinase-regulated signalling complex. (4/431)

p70 S6 kinase (p70S6K) is an important regulator of cell proliferation. Its activation by growth factor requires phosphorylation by various inputs on multiple sites. Data accumulated thus far support a model whereby p70S6K activation requires sequential phosphorylations at proline-directed residues in the putative autoinhibitory pseudosubstrate domain, as well as threonine 389. Threonine 229, a site in the catalytic loop is phosphorylated by phosphoinositide-dependent kinase 1 (PDK-1). Experimental evidence suggests that p70S6K activation requires a phosphoinositide 3-kinase (PI3-K)-dependent signal(s). However, the intermediates between PI3-K and p70S6K remain unclear. Here, we have identified PI3-K-regulated atypical protein kinase C (PKC) isoform PKCzeta as an upstream regulator of p70S6K. In coexpression experiments, we found that a kinase-inactive PKCzeta mutant antagonized activation of p70S6K by epidermal growth factor, PDK-1, and activated Cdc42 and PI3-K. While overexpression of a constitutively active PKCzeta mutant (myristoylated PKCzeta [myr-PKCzeta]) only modestly activated p70S6K, this mutant cooperated with PDK-1 activation of p70S6K. PDK-1-induced activation of a C-terminal truncation mutant of p70S6K was also enhanced by myr-PKCzeta. Moreover, we have found that p70S6K can associate with both PDK-1 and PKCzeta in vivo in a growth factor-independent manner, while PDK-1 and PKCzeta can also associate with each other, suggesting the existence of a multimeric PI3-K signalling complex. This work provides evidence for a link between a phorbol ester-insensitive PKC isoform and p70S6K. The existence of a PI3-K-dependent signalling complex may enable efficient activation of p70S6K in cells.  (+info)

Activation of serum- and glucocorticoid-regulated protein kinase by agonists that activate phosphatidylinositide 3-kinase is mediated by 3-phosphoinositide-dependent protein kinase-1 (PDK1) and PDK2. (5/431)

The PtdIns(3,4,5)P3-dependent activation of protein kinase B (PKB) by 3-phosphoinositide-dependent protein kinases-1 and -2 (PDK1 and PDK2 respectively) is a key event in mediating the effects of signals that activate PtdIns 3-kinase. The catalytic domain of serum- and glucocorticoid-regulated protein kinase (SGK) is 54% identical with that of PKB and, although lacking the PtdIns(3,4, 5)P3-binding pleckstrin-homology domain, SGK retains the residues that are phosphorylated by PDK1 and PDK2, which are Thr256 and Ser422 in SGK. Here we show that PDK1 activates SGK in vitro by phosphorylating Thr256. We also show that, in response to insulin-like growth factor-1 (IGF-1) or hydrogen peroxide, transfected SGK is activated in 293 cells via a PtdIns 3-kinase-dependent pathway that involves the phosphorylation of Thr256 and Ser422. The activation of SGK by PDK1 in vitro is unaffected by PtdIns(3,4,5)P3, abolished by the mutation of Ser422 to Ala, and greatly potentiated by mutation of Ser422 to Asp (although this mutation does not activate SGK itself). Consistent with these findings, the Ser422Asp mutant of SGK is activated by phosphorylation (probably at Thr256) in unstimulated 293 cells, and activation is unaffected by inhibitors of PtdIns 3-kinase. Our results are consistent with a model in which activation of SGK by IGF-1 or hydrogen peroxide is initiated by a PtdIns(3,4, 5)P3-dependent activation of PDK2, which phosphorylates Ser422. This is followed by the PtdIns(3,4,5)P3-independent phosphorylation at Thr256 that activates SGK, and is catalysed by PDK1. Like PKB, SGK preferentially phosphorylates serine and threonine residues that lie in Arg-Xaa-Arg-Xaa-Xaa-Ser/Thr motifs, and SGK and PKB inactivate glycogen synthase kinase-3 similarly in vitro and in co-transfection experiments. These findings raise the possibility that some physiological roles ascribed to PKB on the basis of the overexpression of constitutively active PKB mutants might be mediated by SGK.  (+info)

The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction. (6/431)

Diabetes affects 3% of the European population and 140 million people worldwide, and is largely a disease of insulin resistance in which the tissues fail to respond to this hormone. This emphasizes the importance of understanding how insulin signals to the cell's interior. We have recently dissected a protein kinase cascade that is triggered by the formation of the insulin 'second messenger' phosphatidylinositide (3,4,5) trisphosphate (PtdIns (3,4,5)P3) and which appears to mediate many of the metabolic actions of this hormone. The first enzyme in the cascade is termed 3-phosphoinositide-dependent protein kinase-1 (PDK1), because it only activates protein kinase B (PKB), the next enzyme in the pathway, in the presence of PtdIns (3,4,5)P3. PKB then inactivates glycogen synthase kinase-3 (GSK3). PDK1, PKB and GSK3 regulate many physiological events by phosphorylating a variety of intracellular proteins. In addition, PKB plays an important role in mediating protection against apoptosis by survival factors, such as insulin-like growth factor-1.  (+info)

PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2. (7/431)

BACKGROUND: Protein kinase B (PKB) is activated by phosphorylation of Thr308 and of Ser473. Thr308 is phosphorylated by the 3-phosphoinositide-dependent protein kinase-1 (PDK1) but the identity of the kinase that phosphorylates Ser473 (provisionally termed PDK2) is unknown. RESULTS: The kinase domain of PDK1 interacts with a region of protein kinase C-related kinase-2 (PRK2), termed the PDK1-interacting fragment (PIF). PIF is situated carboxy-terminal to the kinase domain of PRK2, and contains a consensus motif for phosphorylation by PDK2 similar to that found in PKBalpha, except that the residue equivalent to Ser473 is aspartic acid. Mutation of any of the conserved residues in the PDK2 motif of PIF prevented interaction of PIF with PDK1. Remarkably, interaction of PDK1 with PIF, or with a synthetic peptide encompassing the PDK2 consensus sequence of PIF, converted PDK1 from an enzyme that could phosphorylate only Thr308 of PKBalpha to one that phosphorylates both Thr308 and Ser473 of PKBalpha in a manner dependent on phosphatidylinositol (3,4,5) trisphosphate (PtdIns(3,4,5)P3). Furthermore, the interaction of PIF with PDK1 converted the PDK1 from a form that is not directly activated by PtdIns(3,4,5)P3 to a form that is activated threefold by PtdIns(3,4,5)P3. We have partially purified a kinase from brain extract that phosphorylates Ser473 of PKBalpha in a PtdIns(3,4,5)P3-dependent manner and that is immunoprecipitated with PDK1 antibodies. CONCLUSIONS: PDK1 and PDK2 might be the same enzyme, the substrate specificity and activity of PDK1 being regulated through its interaction with another protein(s). PRK2 is a probable substrate for PDK1.  (+info)

Mutational analysis of the coding regions of the genes encoding protein kinase B-alpha and -beta, phosphoinositide-dependent protein kinase-1, phosphatase targeting to glycogen, protein phosphatase inhibitor-1, and glycogenin: lessons from a search for genetic variability of the insulin-stimulated glycogen synthesis pathway of skeletal muscle in NIDDM patients. (8/431)

The finding of a reduced insulin-stimulated glucose uptake and glycogen synthesis in the skeletal muscle of glucose-tolerant first-degree relatives of patients with NIDDM, as well as in cultured fibroblasts and skeletal muscle cells isolated from NIDDM patients, has been interpreted as evidence for a genetic involvement in the disease. The mode of inheritance of the common forms of NIDDM is as yet unclear, but the prevailing hypothesis supports a polygenic model. In the present study, we tested the hypothesis that the putative inheritable defects of insulin-stimulated muscle glycogen synthesis might be caused by genetic variability in the genes encoding proteins shown by biochemical evidence to be involved in insulin-stimulated glycogen synthesis in skeletal muscle. In 70 insulin-resistant Danish NIDDM patients, mutational analysis by reverse transcription-polymerase chain reaction-single strand conformation polymorphism-heteroduplex analysis was performed on genomic DNA or skeletal muscle-derived cDNAs encoding glycogenin, protein phosphatase inhibitor-1, phophatase targeting to glycogen, protein kinase B-alpha and -beta, and the phosphoinositide-dependent protein kinase-1. Although a number of silent variants were identified in some of the examined genes, we found no evidence for the hypothesis that the defective insulin-stimulated glycogen synthesis in skeletal muscle in NIDDM is caused by structural changes in the genes encoding the known components of the insulin-sensitive glycogen synthesis pathway of skeletal muscle.  (+info)

Phosphoinositide-dependent protein kinase 1 (PDK1) is a protein kinase that phosphorylates and activates several other protein kinases from the AGC group (which includes PKA, PKG and PKC), to which PDK1 also belongs. Recent data suggests that PDK1 specificity is achieved by regulation of its interac …
Protein target information for Chain A, 3-phosphoinositide-dependent protein kinase 1 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
Protein target information for Chain A, 3-phosphoinositide-dependent protein kinase 1 (human). Find diseases associated with this biological target and compounds tested against it in bioassay experiments.
TY - JOUR. T1 - Peroxovanadate induces tyrosine phosphorylation of phosphoinositide-dependent protein kinase-1 potential involvement of src kinase. AU - Grillo, S. AU - Gremeaux, T. AU - Casamayor, A. AU - Alessi, DR. AU - Le, Marchand-Brustel Y. AU - Tanti, JF.. PY - 2000/1/1. Y1 - 2000/1/1. M3 - Article. VL - 267. SP - 6642. EP - 6649. IS - 22. ER - ...
NAC, a common dietary supplement and an antioxidant membrane-permeable metal-binding compound, has been shown to inhibit inflammatory responses, tumor growth including lung cancer [13, 14]. However, the mechanisms by which this reagent in control of NSCLC cell growth has not been well elucidated. We have found that NAC inhibited NSCLC cell proliferation through reduction of PDK1, a kinase and master regulator of a number of downstream signal cascades that are involved in suppression of apoptosis and promotion of tumor growth including lung cancer [4, 15]. High expression of PDK1 has been detected in invasive cancers including lung [5] and inhibition of PDK1 in several cancer cells results in significant cell growth inhibition [6]. These observations suggest that PDK1 can be considered as a target for therapies. This result, together with the finding that exogenous PDK1 diminishes the inhibitory effect of NAC on cell growth, indicates an important role of targeting PDK1 in mediating the ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
doi: 10.1016/j.abb.2005.08.012, 10.1002/0471264180.or025.02 oph: A organo-phosphate (P-O) hydroxyl bound to a ketone or aldehyde. Synthetic intermediate and precursor to organo-phosphate agents known as AChE inhibitors. Reaction is catalyzed by the Organo-Phosphate Hydrolase enzyme, thus a (Mg)ATP-dependent ligase. See related DOIs above. dfp (Isoflurophate): http://www.drugbank.ca/drugs/DB00677, Wikipedia EC (DFPase) http://www.genome.jp/dbget-bin/www_bget?ec: EC (Parathion hydrolase) http://www.uniprot.org/uniprot/P0A433, http://www.drugbank.ca/drugs/DB02138 HMDB keywords: functionalized diphosphine, chim trills, DFP, Paraoxon Reaction type: oxidative desulfuration (BioCyc) Related: 3-phosphoinositide-dependent protein kinase 1, Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform Regulation of 3-Phosphoinositide-dependent Protein Kinase-1 (PDK1) by Src Involves Tyrosine Phosphorylation of PDK1 and Src Homology 2 Domain Binding ...
TY - JOUR. T1 - PDK1 in apical signaling endosomes participates in the rescue of the polarity complex atypical PKC by intermediate filaments in intestinal epithelia. AU - Mashukova, Anastasia. AU - Forteza, Radia. AU - Wald, Flavia A.. AU - Salas, Pedro J. PY - 2012/5/1. Y1 - 2012/5/1. N2 - Phosphorylation of the activation domain of protein kinase C (PKC) isoforms is essential to start a conformational change that results in an active catalytic domain. This activation is necessary not only for newly synthesized molecules, but also for kinase molecules that become dephosphorylated and need to be refolded and rephosphorylated. This rescuemechanism is responsible for the maintenance of the steady-state levels of atypical PKC (aPKC [PKCι/λ and ζ]) and is blocked in inflammation. Although there is consensus that phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for newly synthesized molecules, it is unclear what kinase performs that function during the rescue and where ...
TY - JOUR. T1 - Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA. T2 - Potential mechanism contributing to increased lipid oxidation in insulin- resistant subjects. AU - Majer, Martin. AU - Popov, Kirill M.. AU - Harris, Robert A.. AU - Bogardus, Clifton. AU - Prochazka, Michal. PY - 1998/10. Y1 - 1998/10. N2 - Oxidative metabolism of glucose is regulated by pyruvate dehydrogenase (PDH) that can be inhibited by isoforms of PDH kinase (PDK). Recently, increased PDK activity has been implicated in the pathogenesis of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) in obese subjects. Using quantitative RT-PCR, we measured mRNA of PDK2 and PDK4 isoforms in skeletal muscle biopsies from nondiabetic Pima Indians, a population with a high prevalence of NIDDM associated with obesity. PDK2 and PDK4 mRNAs were positively correlated with fasting plasma insulin concentration, 2-h plasma insulin concentration in response to oral glucose, and percentage body fat, whereas ...
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK ...
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. Activation of Akt also results in the translocation of GLUT4 vesicles from their intracellular pool to the plasma membrane, where they allow uptake of glucose into the cell. Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. Other signal transduction proteins interact with IRS including GRB2. GRB2 is part of the cascade including SOS, RAS, RAF and MEK ...
The phosphatidylinositol 3-kinases (PI3K) are a family of lipid kinases that are involved in a wide range of cancer-related signaling pathways, including proliferation, survival, motility, differentiation, cytoskeletal rearrangement, and angiogenesis ( 1- 3). PI3Ks are categorized into three families according to their subunit structure, regulation, and substrate selectivity ( 4). Class IA PI3K, which comprises a 110-kDa catalytic subunit and a regulatory subunit of 85, 55, or 50 kDa, plays an important role in regulating proliferation, motility, and survival ( 5, 6). AKT, the major downstream effector of PI3K, is activated by phosphoinositide-dependent protein kinase 1, which is recruited and phosphorylated by activation of PI3K. The PI3K/AKT signaling pathway regulates several transcriptional factors, including the forkhead transcription factor FKHR and nuclear factor-κB, which are involved in cell cycle control and apoptosis ( 7- 11). The PI3K/AKT pathway has also been reported to regulate ...
Spermatogonial stem cells (SSCs) capable of self-renewal and differentiation are the foundation for spermatogenesis. Although several factors important for these processes have been identified, the fundamental mechanisms regulating SSC self-renewal and differentiation remain unknown. Here, we investigated a role for the Foxo transcription factors in mouse spermatogenesis and found that Foxo1 specifically marks mouse gonocytes and a subset of spermatogonia with stem cell potential. Genetic analyses showed that Foxo1 was required for both SSC homeostasis and the initiation of spermatogenesis. Combined deficiency of Foxo1, Foxo3, and Foxo4 resulted in a severe impairment of SSC self-renewal and a complete block of differentiation, indicating that Foxo3 and Foxo4, although dispensable for male fertility, contribute to SSC function. By conditional inactivation of 3-phosphoinositide-dependent protein kinase 1 (Pdk1) and phosphatase and tensin homolog (Pten) in the male germ line, we found that PI3K ...
Spermatogonial stem cells (SSCs) capable of self-renewal and differentiation are the foundation for spermatogenesis. Although several factors important for these processes have been identified, the fundamental mechanisms regulating SSC self-renewal and differentiation remain unknown. Here, we investigated a role for the Foxo transcription factors in mouse spermatogenesis and found that Foxo1 specifically marks mouse gonocytes and a subset of spermatogonia with stem cell potential. Genetic analyses showed that Foxo1 was required for both SSC homeostasis and the initiation of spermatogenesis. Combined deficiency of Foxo1, Foxo3, and Foxo4 resulted in a severe impairment of SSC self-renewal and a complete block of differentiation, indicating that Foxo3 and Foxo4, although dispensable for male fertility, contribute to SSC function. By conditional inactivation of 3-phosphoinositide-dependent protein kinase 1 (Pdk1) and phosphatase and tensin homolog (Pten) in the male germ line, we found that PI3K ...
Molecular association of cancer cell metastasis with signaling pathways has been explicated so as to aid in the development of new prognostic models for better cancer therapies. However, those metastatic signaling pathways are barely explored to take account of the functions of enzymes involved in cellular metabolism. Particularly, the metabolic enzymes in de novo purine biosynthesis have been overlooked for their potential roles in cancer cell metastasis even though they have been successfully validated anti-cancer drug targets. Meanwhile, several lines of recent discoveries on de novo purine biosynthesis suggest that the spatiotemporal assembly of purine biosynthetic enzymes, the purinosome, is under controls of signaling pathways in cancer cells. The results of the inquiry reveal an unanticipated mechanism of action of 3-phosphoinositide-dependent protein kinase 1 (PDK1) signaling pathways in regulation of purine biosynthesis in an Akt-independent manner. Considering the biological action of ...
TY - JOUR. T1 - Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates. AU - Komander, David. AU - Fairservice, Alison. AU - Deak, Maria. AU - Kular, Gursant S.. AU - Prescott, Alan R.. AU - Downes, C. Peter. AU - Safrany, Stephen T.. AU - Alessi, Dario R.. AU - Van Aalten, Daan M.F.. PY - 2004/10/13. Y1 - 2004/10/13. N2 - 3-phosphoinositide-dependent protein kinase-1 (PDK1) phosphorylates and activates many kinases belonging to the AGC subfamily. PDK1 possesses a C-terminal pleckstrin homology (PH) domain that interacts with PtdIns(3,4,5)P3/PtdIns(3,4)P2 and with lower affinity to PtdIns(4,5)P2. We describe the crystal structure of the PDK1 PH domain, in the absence and presence of PtdIns(3,4,5)P3 and Ins(1,3,4,5)P4. The structures reveal a budded PH domain fold, possessing an N-terminal extension forming an integral part of the overall fold, and display an unusually spacious ligand-binding site. Mutagenesis and lipid-binding studies were used to define ...
The function of PI3K-mTOR pathway in regulating NK cell improvement has been extensively reported. However, it stays unclear whether or not NK cell improvement depends upon the protein kinase B (PKB), which hyperlinks PI3K and mTOR, maybe because of the potential redundancy of PKB. PKB has two phosphorylation websites, threonine 308 (T308) and serine 473 (S473), which may be phosphorylated by phosphoinositide-dependent protein kinase-1 (PDK1) and mTORC2, respectively. In this research, we established a mouse mannequin wherein PKB was inactivated by the deletion of PDK1 and Rictor, a key element of mTORC2, respectively.. We discovered that the only deletion of PDK1 or Rictor may result in a major defect in NK cell improvement, whereas mixed deletion of PDK1 and Rictor severely hindered NK cell improvement on the early stage. Notably, ectopic expression of myristoylated PKB considerably rescued this defect. In phrases of mechanism, in PDK1/Rictor-deficient NK cells, E4BP4, a transcription issue ...
The function of PI3K-mTOR pathway in regulating NK cell improvement has been extensively reported. However, it stays unclear whether or not NK cell improvement depends upon the protein kinase B (PKB), which hyperlinks PI3K and mTOR, maybe because of the potential redundancy of PKB. PKB has two phosphorylation websites, threonine 308 (T308) and serine 473 (S473), which may be phosphorylated by phosphoinositide-dependent protein kinase-1 (PDK1) and mTORC2, respectively. In this research, we established a mouse mannequin wherein PKB was inactivated by the deletion of PDK1 and Rictor, a key element of mTORC2, respectively.. We discovered that the only deletion of PDK1 or Rictor may result in a major defect in NK cell improvement, whereas mixed deletion of PDK1 and Rictor severely hindered NK cell improvement on the early stage. Notably, ectopic expression of myristoylated PKB considerably rescued this defect. In phrases of mechanism, in PDK1/Rictor-deficient NK cells, E4BP4, a transcription issue ...
Forkhead in rhabdomyosarcoma (FKHR) is a transcription factor that has been implicated in the control of gene expression by insulin, as well as the regulation of apoptosis by survival factors. These signals trigger the protein kinase B (PKB)-catalysed phosphorylation of FKHR at three residues (Thr24, Ser256 and Ser319) by a phosphoinositide 3-kinase-dependent pathway that results in the nuclear exit and inactivation of this transcription factor. Here, we have identified a conserved residue (Ser329) as a novel in vivo phosphorylation site on FKHR. Ser329 phosphorylation also decreases the ability of FKHR to stimulate gene transactivation and reduces the proportion of FKHR present in the nucleus. However, unlike the residues targetted by PKB, Ser329 is phosphorylated in unstimulated HEK-293cells, and phosphorylation is not increased by stimulation with insulin-like growth factor-1 or by transfection with 3-phosphoinositide-dependent protein kinase-1. We have also purified a protein kinase to near ...
1OKZ: Structural Basis for Ucn-01 (7-Hydroxystaurosporine) Specificity and Pdk1 (3-Phosphoinositide-Dependent Protein Kinase-1) Inhibition
1OKY: Structural Basis for Ucn-01 (7-Hydroxystaurosporine) Specificity and Pdk1 (3-Phosphoinositide-Dependent Protein Kinase-1) Inhibition
antibody-antibodies.com is the marketplace for research antibodies. Find the right antibody for your research needs. 3-Phosphoinositide-dependent PDK1 negatively regulates transforming growth factor-beta-induced signaling in a kinase-dependent manner through physical interaction with Smad proteins.
Phosphoinositide-dependent kinase 1 (PDK1) is the master regulator of at least 23 other AGC kinases whose downstream signalling has often been implicated in various diseases and in particular in cancer. Therefore there has been great interest in determining how PDK1 is controlled and how it regulates its substrates spatially and temporally. The understanding of these mechanisms could offer new possibilities for therapeutic intervention. Over the years, a more comprehensive view of the mechanisms involved in the regulation of PDK1 has emerged and these comprise serine/threonine as well as tyrosine phosphorylation, subcellular localization, regulator binding and conformation status. In the present review, we discuss how various molecular mechanisms are together responsible for the conformational regulation behind the activation of PDK1 in cells. ...
Phosphatidylinositol (PI) 3-kinase mediates multiple pathways that regulate many aspects of the cell including rate of metabolism, survival, migration, and proliferation. apoptosis, suggesting that FLII itself is also a survival element. These findings support the model that CISK phosphorylates FLII and activates nuclear receptor transcription and suggest a new cell survival signaling pathway mediated by PI 3-kinase and CISK. Cell death and survival are tightly controlled throughout development, through the action of numerous factors and pathways (1C6). Of these, PI2 3-kinase and its own downstream effectors are being among the most studied widely. PI 3-kinase pathway is vital for success and proliferation of mammalian cells and continues to be implicated in cancers (7C10). Through the legislation of D3-phosphoinositol amounts in cells, PI 3-kinases control the experience of 3-phosphoinositide-dependent kinase and associates from the AGC (cAMP-dependent proteins kinase/proteins kinase G/proteins ...
G-protein-coupled receptors (GPCRs) activate the epidermal growth factor receptor (EGFR) and mediate EGFR-independent signaling pathways to promote the growth of a variety of cancers including head and neck squamous cell carcinoma (HNSCC). Identification of the common signaling mechanisms involved in GPCR-induced EGFR-dependent and independent processes will facilitate the development of more therapeutic strategies. In this study, we hypothesized that phosphoinositide-dependent kinase 1 (PDK1) contributes to GPCR-EGFR crosstalk and signaling in the absence of EGFR and suggests that inhibition of the PDK1 pathway may be effective in the treatment of HNSCC. The contribution of PDK1 to the EGFR-dependent and independent signaling in HNSCC was determined using RNAi, a kinase-dead mutant and pharmacological inhibition. In vivo xenografts studies were also performed to determine the efficacy of targeting PDK1 alone or in combination with the FDA-approved EGFR inhibitor cetuximab. PDK1 contributed to ...
Aberrant activation of the intracellular PI3K-AKT-mTOR signaling pathway, which regulates critical processes such as cell cycle and survival, is one of the most common occurrences in human cancers and has been the focus of targeted therapy development. However, inhibitors targeting PI3K, AKT, or mTOR have shown limited clinical benefit. To identify new regulators of the PI3K-AKT pathway, Wheeler and colleagues screened 7,450 shRNAs for kinases or GTPases that affect AKT phosphorylation at serine 473 (S473), and identified 29 genes that had not been previously implicated in PI3K-AKT signaling, as well as genes known to regulate AKT phosphorylation. Of the 29 genes, the most-represented functional group was the RAB GTPases, which regulate endomembrane trafficking. Knockdown of RAB35, one of the five RAB GTPases identified in the screen, in multiple cell lines resulted in decreased AKT phosphorylation at S473 as well as diminished phosphorylation of phosphoinositide-dependent kinase 1 (PDK1) and ...
Phosphoinositides have traditionally been known to be important in the generation of the second messengers inositol 1,4,5,-triphosphate and diacylglycerol. Recently, it was demonstrated that in yeast and animals, phosphoinositides themselves are regulators of a wide variety of cellular processes, such as signal transduction, actin cytoskeleton organization, vesicle trafficking, and activation of proteins such as phosphoinositide-dependent kinase 1 and phospholipase D (Martin, 1998; Takenawa and Itoh, 2001). In plant cells, all phosphoinositide forms except phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3] have been identified, and they have been suggested to play important roles in vesicle trafficking (Matsuoka et al., 1995; Kim et al., 2001), pollen tube growth (Kost et al., 1999), and stress and hormone responses (Mikami et al., 1998; Meijer et al., 1999, 2001; Pical et al., 1999; DeWald et al., 2001). PtdIns(4,5)P2 has been shown to bind profilin (Kovar et al., 2001) and to regulate ...
It is likely that the loss of Pten found in the tumors of PTEN+/− mice leads to increased levels of PtdIns(3,4,5)P3, which in turn is able to activate AKT, 3-phosphoinositide-dependent kinase 1, S6K, mTOR, and many other proteins. In combination, these activated proteins probably contribute to the transformation and increased tumor proliferation that was observed in a variety of organs (Figs. 1 and 2). Of these activated proteins, S6K is likely to play a major role in the progression of the cell cycle into the S phase. Microinjection of anti-S6K antibodies into quiescent rat embryo fibroblasts prevents the mitogenic effect of serum (32, 33). In T cells, which are unable to proliferate in the presence of rapamycin, a rapamycin-resistant allele of S6K is sufficient to rescue the activation of an E2F reporter (42). S6K1−/− mouse embryonic stem cells have an elevated proportion of cells in G0/G1 and slower proliferation relative to wild type (10). Finally, dTOR mutation is associated with ...
An understanding of the molecular basis for the survival of tumor cells through resistance to apoptosis is critical for the development of rational and suitably targeted antineoplastic therapies. An increasing number of studies have shown that activation of the PI3-K/Akt survival pathway plays an important role in BCR-ABL-mediated leukemogenesis. More recently, the significance of Akt activation in CML was investigated in the context of imatinib resistance. Interestingly, whereas the BCR-ABL T315I imatinib-resistant mutation is refractory to the combination of imatinib and numerous compounds, inhibition of Akt signaling with a phosphoinositide-dependent kinase-1 inhibitor, OSU-03012, synergizes with imatinib to induce apoptosis in BCR-ABL T315I cells ( 46). These studies suggest that Akt activation is an important event even in imatinib-resistant CML.. The FoxO3a transcription factor represents a critical substrate that is inhibited by Akt during growth factor-induced survival ( 25). We and ...
Phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] is a minor phospholipid in the cytoplasmic leaflet of the plasma membrane. Depletion of PI(4,5)P2 via phospholipase C-mediated hydrolysis leads to a decrease in exocytosis and alters electrical excitability in neurons. Restoration of PI(4,5)P2 is ess …
PS10 是一种新型,有效且具有 ATP 竞争性的广谱 PDK 抑制剂,可抑制所有 PDK 同工型,对 PDK2,PDK4,PDK1 和 PDK3 的 IC50 分别为 0.8 μM,0.76 μM,2.1 μM 和 21.3 μM。 PS10 对 PDK2 (Kd= 239 nM) 的亲和力高于对 Hsp90 (Kd= 47 μM)。 PS10 改善葡萄糖耐量,刺激饮食引起的肥胖症中的心肌碳水化合物氧化。 PS10 具有研究糖尿病性心肌病的潜力 ...
Persistently hyperphosphorylated Akt contributes to human oncogenesis and resistance to therapy. Triciribine (TCN) phosphate (TCN-P), the active metabolite of the Akt phosphorylation inhibitor TCN, is in clinical trials, but the mechanism by which TCN-P inhibits Akt phosphorylation is unknown. Here we show that in vitro, TCN-P inhibits neither Akt activity nor the phosphorylation of Akt S473 and T308 by mammalian target of rapamycin or phosphoinositide-dependent kinase 1. However, in intact cells, TCN inhibits EGF-stimulated Akt recruitment to the plasma membrane and phosphorylation of Akt. Surface plasmon resonance shows that TCN, but not TCN, binds Akt-derived pleckstrin homology (PH) domain (K(D) 690 nM). Furthermore, nuclear magnetic resonance spectroscopy shows that TCN-P, but not TCN, binds to the PH domain in the vicinity of the PIP3-binding pocket. Finally, constitutively active Akt mutants, Akt1-T308D/S473D and myr-Akt1, but not the transforming mutant Akt1-E17K, are resistant to TCN ...
(2003) Bögre et al. Trends in Plant Science. Lipid-derived signals are central to regulating a multitude of cellular processes but, in plants, little is known of the downstream signalling pathways. The Arabidopsis 3-phosphoinositide-dependent...
Macrophage polarization is a process by which macrophages carry out various functional programs responding to signals. Pyruvate Dehydrogenase Kinase (PDK) is a kinase, phosphorylates pyruvate dehydrogenase with ATP to cause…. Read More Read More. ...
Bioz Stars score, Techniques, Protocol Conditions and more for Agc 017, supplied by Alomone Labs. Data for Agc 017 gathered from related PubMed articles.
TY - JOUR. T1 - PDK1-Foxo1 in agouti-related peptide neurons regulates energy homeostasis by modulating food intake and energy expenditure. AU - Cao, Yongheng. AU - Nakata, Masanori. AU - Okamoto, Shiki. AU - Takano, Eisuke. AU - Yada, Toshihiko. AU - Minokoshi, Yasuhiko. AU - Hirata, Yukio. AU - Nakajima, Kazunori. AU - Iskandar, Kristy. AU - Hayashi, Yoshitake. AU - Ogawa, Wataru. AU - Barsh, Gregory S.. AU - Hosoda, Hiroshi. AU - Kangawa, Kenji. AU - Itoh, Hiroshi. AU - Noda, Tetsuo. AU - Kasuga, Masato. AU - Nakae, Jun. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2011. Y1 - 2011. N2 - Insulin and leptin intracellular signaling pathways converge and act synergistically on the hypothalamic phosphatidylinositol-3-OH kinase/3-phosphoinositide-dependent protein kinase 1 (PDK1). However, little is known about whether PDK1 in agouti-related peptide (AGRP) neurons contributes to energy homeostasis. We generated AGRP neuron-specific PDK1 knockout (AGRPPdk1-/-) mice and ...
Mutations in the coactivator CREB-binding protein (CBP) are a major cause of the human skeletal dysplasia Rubinstein-Taybi syndrome (RTS); however, the mechanism by which these mutations affect skeletal mineralization and patterning is unknown. Here, we report the identification of 3-phosphoinositide-dependent kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate that its functions map to both osteoprogenitor cells and mature osteoblasts. In osteoblasts, PDK1 activated the CREB/CBP complex, which in turn controlled runt-related transcription factor 2 (RUNX2) activation and expression of bone morphogenetic protein 2 (BMP2). These pathways also operated in vivo, as evidenced by recapitulation of RTS spectrum phenotypes with osteoblast-specific Pdk1 deletion in mice (Pdk1osx mice) and by the genetic interactions observed in mice heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or Creb deletion. Finally, treatment of Pdk1osx and Cbp+/- embryos with BMPs in utero ...
We first evaluated the phosphorylation state of Akt at Ser-473, the site of phosphorylation by MAPKAPK-2, which has been shown to be critical for the generation of high levels of Akt enzyme activity. 15 32 33 Several other kinases have also been reported to phosphorylate Akt at Ser-473, including integrin-linked kinase (ILK), 34 35 36 3-phosphoinositide-dependent kinase-1 (PDK-1) 35 and DNA-dependent protein kinase (DNA-PK). 37 Our data showed two distinct phases of Ser-473 Akt modulation during photoreceptor degeneration: the first one was characterized by the inactivation of Akt, and extended from early onset (13 days) to the peak of photoreceptor apoptosis (15 days), and the following one displayed a striking Akt activation during the period when most photoreceptors have degenerated. The fact that Akt activation levels were decreased and no immunoreactivity of the active form was detected at the photoreceptor level, strongly suggests that the Akt survival signaling pathway was inhibited ...
Hu X, Xu X, Lu Z, Zhang P, Fassett J, Zhang Y, Xin Y, Hall JL, Viollet B, Bache RJ, et al. AMP activated protein kinase-α2 regulates expression of estrogen-related receptor-α, a metabolic transcription factor related to heart failure development. Hypertension [Internet]. 2011;(4):696-703.
CMPD-1 is a non-ATP-competitive, selective inhibitor of p38α-mediated MK2a (mitogen-activated protein kinase-2a) phosphorylation (apparent Ki = 330 nM).
Pdpk1 - Pdpk1 (untagged ORF) - Rat 3-phosphoinositide dependent protein kinase-1 (Pdpk1), (10 ug) available for purchase from OriGene - Your Gene Company.
GSK690693 is a pan-Akt inhibitor targeting Akt1, 2, 3 with IC50 values of 2, 13 and 9 nM, respectively [1, 2]. In addition, it also inhibits AMPK (IC50=50 nM), DAPK3 (IC50=81 nM), PAK4, 5, and 6 (IC50=10, 52, 6 nM), as well as the members of AGC kinase fa
电子快讯 欲获得最新ADI产品、设计工具、培训与活动的相关新闻与文章,请从我们的在线快讯中选出您感兴趣的产品类别,每月或每季度都会发送至您的收件箱。 ...
Title:Mass Spectrometry-based Label-free Quantitative Proteomic Analysis of CCl4-induced Acute Liver Injury in Mice Intervened by Total Glycosides from Ligustri Lucidi Fructus. VOLUME: 17 Author(s):Qian Lu, Hai-Zhu Xing and Nian-Yun Yang*. Affiliation:Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Jiangsu Plant Medicine Research and Development Center, Nanjing University of Chinese Medicine, Nanjing 210023. Keywords:Ligustri Lucidi Fructus, Proteome, 3-Phosphoinositide-dependent protein kinase 1, Insulin-Like growth factor 1, Autophagy ...
We have recently shown that parathyroid hormone-related protein (PTHrP), a cytokine-like polyprotein, is critical for human renal cell carcinoma (RCC) growth by inhibiting tumor cell apoptosis. Here, we have explored mechanisms by which PTHrP controls tumor cell survival. Using specific inhibitors of phosphoinositide 3-kinase (PI3K) and depletion of Akt kinase by RNA interference, we established that PTHrP is one of the main factor involved in the constitutive activation of this pathway in human RCC, independently of von Hippel-Lindau (VHL) tumor suppressor gene expression. Interestingly, PTHrP induced phosphorylation of Akt at S473 but had no influence on phosphorylation at T308. Through transfection with integrin-linked kinase (ILK) constructs and RNA interference, we provide evidence that ILK is involved in human RCC cell survival. PTHrP activates ILK which then acts as a phosphoinositide-dependent kinase (PDK)-2 or a facilitator protein to phosphorylate Akt at S473. Among other kinases ...
TY - JOUR. T1 - High-Resolution Structure of the Pleckstrin Homology Domain of Protein Kinase B/Akt Bound to Phosphatidylinositol (3,4,5)-Trisphosphate. AU - Thomas, Christine C.. AU - Deak, Maria. AU - Alessi, Dario R.. AU - van Aalten, Daan M. F.. PY - 2002/7/23. Y1 - 2002/7/23. N2 - The products of PI 3-kinase activation, PtdIns(3,4,5)P3 and its immediate breakdown product PtdIns(3,4)P2, trigger physiological processes, by interacting with proteins possessing pleckstrin homology (PH) domains [1, 2]. One of the best characterized PtdIns(3,4,5)P3/PtdIns(3,4)P2 effector proteins is protein kinase B (PKB), also known as Akt [3-5]. PKB possesses a PH domain located at its N terminus, and this domain binds specifically to PtdIns(3,4,5)P3 and PtdIns(3,4)P2 with similar affinity [6, 7]. Following activation of PI 3-kinase, PKB is recruited to the plasma membrane by virtue of its interaction with PtdIns(3,4,5)P3/PtdIns(3,4)P2 [8-10]. PKB is then activated by the 3-phosphoinositide-dependent pro-tein ...
What does Computing & IT PDK stand for? Hop on to get the meaning of PDK. The Computing & IT Acronym /Abbreviation/Slang PDK means Portal Development Kit. by AcronymAndSlang.com
Use Bio-Rads PrimePCR assays, controls, templates for your target gene. Every primer pair is optimized, experimentally validated, and performance guaranteed.
PDK Selayang (Pusat Pemulihan Dalam Komuniti Selayang) telah ditubuhkan pada 1hb Sept 1991, oleh sekumpulan ibubapa kepada kanak-kanak kurang upaya (pada masa tersebut dipanggil sebagai kanak-kanak istimewa) yang anak-anak mereka telah dikeluarkan dari pembelajaran wajib di sekolah-sekolah aliran perdana di Selayang, dengan alasan mereka (OKU tersebut) tidak boleh belajar. Alasan sebenar Guru Besar sekolah-sekolah tersebut ialah mereka takut graf pencapaian sekolah akan menurun ...
PROFESI-UNM.COM - Himpunan Mahasiswa Jurusan (HMJ) Pendidikan Khusus (PKh) Fakultas Ilmu Pengetahuan Universitas Negeri Makassar (FIP-UNM) gelar bakti sosial dengan tema Menjalin ...
"Phosphoinositide-dependent protein kinase 1 is a potential novel therapeutic target in mantle cell lymphoma". Experimental ... The phosphoinositide 3-kinase/3-phosphoinositide-dependent kinase 1 (PDK1)/AKT signaling pathway plays a role in cancer cell ... BX-912 is a small molecule that inhibits 3-phosphoinositide dependent protein kinase-1. ... "Novel small molecule inhibitors of 3-phosphoinositide-dependent kinase-1". The Journal of Biological Chemistry. 280 (20): 19867 ...
"The adapter protein ZIP binds Grb14 and regulates its inhibitory action on insulin signaling by recruiting protein kinase Czeta ... This protein likely has an inhibitory effect on receptor tyrosine kinase signaling and, in particular, on insulin receptor ... Growth factor receptor-bound protein 14 is a protein that in humans is encoded by the GRB14 gene. The product of this gene ... belongs to a small family of adapter proteins that are known to interact with a number of receptor tyrosine kinases and ...
... phosphoinositide dependent protein kinase 1 (PDK1) acts as a master regulator. PDK1 phosphorylates and activates D6PK at the ... F-box proteins target other proteins for degradation via the ubiquitin degradation pathway. When TIR1/ AFB proteins bind to ... In addition, other AGC kinases, such as D6PK, phosphorylate and activate PIN transporters. AGC kinases, including PINOID and ... Krecek P, Skupa P, Libus J, Naramoto S, Tejos R, Friml J, Zazímalová E (Dec 29, 2009). "The PIN-FORMED (PIN) protein family of ...
These two paralogue proteins self-assemble in higher order structure helices and bind preferentially to phosphoinositide- ... BAR) Bin-Amphiphysin-RVS Slm1 Phosphoinositide PI4,5P(2) binding protein, forms a complex with Slm2p; acts downstream of Mss4p ... These are large protein complexes composed primarily of subunits of two Bin-Amphiphysin-RVS (BAR) domain containing proteins ... phosphorylated by the TORC2 complex Slm2 Phosphoinositide PI4,5P(2) binding protein, forms a complex with Slm1p; acts ...
... phosphoinositide-dependent protein kinase-1 and regulates glucose-induced biological responses in pancreatic beta-cells". ... miR-375 has been shown to target the MTPN gene, which encodes the myotrophin protein, that regulates hormone release and ... protein expression". Int J Clin Exp Pathol. 3 (3): 254-264. PMC 2836503. PMID 20224724. El Ouaamari A, Baroukh N, Martens GA, ... 394 (3): 623-627. doi:10.1016/j.bbrc.2010.03.036. PMID 20226166. Poy MN, Hausser J, Trajkovski M, Braun M, Collins S, Rorsman P ...
... phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα. Current Biology. 1997;7(4). ... phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα. Current Biology. 1997;7(4). ... proteins activation loop and S437 in the proteins hydrophobic domain are phosphorylated by Phosphoinositide-dependent kinase-1 ... High Affinity Binding of Inositol Phosphates and Phosphoinositides to the Pleckstrin Homology Domain of RAC/Protein Kinase B ...
Hetz CA, Hunn M, Rojas P, Torres V, Leyton L, Quest AF (December 2002). "Caspase-dependent initiation of apoptosis and necrosis ... Snider AJ, Orr Gandy KA, Obeid LM (June 2010). "Sphingosine kinase: Role in regulation of bioactive sphingolipid mediators in ... These sphingolipid-based microdomains, or "lipid rafts" were originally proposed to sort membrane proteins along the cellular ... It may be phosphorylated by ceramide kinase to form ceramide-1-phosphate. Alternatively, it may be glycosylated by ...
... and the lipid dependent protein kinase B (PKB) signaling pathway increases the survival of lymphocytes and other immune cells ... Phosphoinositide 3-kinase (PI3K) and the GTPase RAC are responsible of the lymphocytes migration and their interactions with ... All the intracellular functions occur via the interaction with Gαi and Gαo: these two proteins recruit other proteins for ... mitogen-activated protein kinase pathway". J. Biol. Chem. 271 (19): 11272-9. doi:10.1074/jbc.271.19.11272. PMID 8626678. " ...
"Rab2 interacts directly with atypical protein kinase C (aPKC) iota/lambda and inhibits aPKCiota/lambda-dependent glyceraldehyde ... protein kinase C inhibitor bisindolyl maleimide 2 binds with reversed orientations to different conformations of protein kinase ... a novel protein that specifically interacts with the zinc finger domain of the atypical protein kinase C isotype lambda/iota ... "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase". Science. 253 (5018): ...
Phosphoinositide dependent protein kinase 1 (PDK1), also from the AGC family, is a critical activator of AGC kinases and is ... Polar auxin transport can be regulated by reversible protein phosphorylation; protein kinases and protein phosphatases mediate ... some membrane transport protein. Two protein families: The PIN proteins and ABCB (PGP proteins) transporters function as "auxin ... and phosphorylated PIN proteins can be oppositely dephosphorylated by Protein Phosphatase 2A (PP2A), Protein Phosphatase 1 (PP1 ...
... and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain ... The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling ... C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may ... kinase and mitogen-activated protein (MAP) kinase pathways". J. Leukoc. Biol. 78 (4): 1016-23. doi:10.1189/jlb.0105056. PMID ...
... and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels ... The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling ... C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, ... "Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and - ...
... and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is not sensitive to nanomolar levels ... This protein was shown to be able to be activated by insulin and may be involved in integrin-dependent signaling. Three ... The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling ... "Extracellular HIV-1 Tat protein induces a rapid and selective activation of protein kinase C (PKC)-alpha, and -epsilon and - ...
Its activation also induces mitogen-activated protein kinases (MAPK) activation along with phosphoinositide 3-kinase activation ... showed that LTA causes an IL-10-dependent inhibition of CD4 T-cell expansion and function by up-regulating PD-1 levels on ...
Phosphoinositide-dependent kinase-1, EZR, PODXL, Cystic fibrosis transmembrane conductance regulator and PLCB3. Solute carrier ... also known as tyrosine kinase activator protein 1 (TKA-1) or SRY-interacting protein 1 (SIP-1) is a protein that in humans is ... "NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ... "NHE3 kinase A regulatory protein E3KARP binds the epithelial brush border Na+/H+ exchanger NHE3 and the cytoskeletal protein ...
... phosphoinositide dependent kinase 1 (PDPK1 at threonine 308 in Akt1 and threonine 309 in Akt2) and the mammalian target of ... including integrin-linked kinase (ILK) and mitogen-activated protein kinase-activated protein kinase-2 (MAPKAPK2) can also ... Protein kinase B (PKB), also known as Akt, is the collective name of a set of three serine/threonine-specific protein kinases ... There are three different genes that encode isoforms of Protein kinase B. These three genes are referred to as AKT1, AKT2, and ...
... has been shown to interact with: AKAP9, Actinin, alpha 1, CCDC85B, NEFL, NEUROD2 Phosphoinositide-dependent ... This kinase is activated by Rho family of small G proteins and may mediate the Rho-dependent signaling pathway. This kinase can ... "A novel protein kinase with leucine zipper-like sequences: its catalytic domain is highly homologous to that of protein kinase ... Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene. The protein encoded by this gene ...
... through a protein kinase C-dependent mechanism". The Biochemical Journal. 466 (2): 379-90. doi:10.1042/BJ20140881. PMID ... membrane-bound receptor for activated protein kinase C proteins). The protein kinase C enzymes are known for their long-term ... In cell biology, Protein kinase C, commonly abbreviated to PKC (EC, is a family of protein kinase enzymes that are ... The consensus sequence of protein kinase C enzymes is similar to that of protein kinase A, since it contains basic amino acids ...
DNA-dependent protein kinase (DNA-PK) and mammalian target of rapamycin (mTOR). They are protein serine/threonine kinases. The ... Likewise, the phosphoinositide-dependent kinase-1 (PDK1 or, rarely referred to as PDPK1) also contains a pleckstrin homology ... leading to the discovery that this phosphoinositide kinase had the unprecedented ability to phosphorylate phosphoinositides on ... Many of these functions relate to the ability of class I PI3Ks to activate protein kinase B (PKB, aka Akt) as in the PI3K/AKT/ ...
"Regulation of cell adhesion and anchorage-dependent growth by a new beta 1-integrin-linked protein kinase". Nature. 379 (6560 ... Phosphoinositide binding motif and extreme N-terminus of kinase catalytic domain. Integrins lack enzymatic activity and depend ... "Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and ... "Inhibition of insulin-induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C". The ...
The protein encoded by this gene is a member of the AKT subfamily of serine/threonine protein kinases. AKT kinases are known to ... AKT-dependent survival pathways in Kaposi's sarcoma cells". J. Biol. Chem. 277 (28): 25195-202. doi:10.1074/jbc.M200921200. ... protein kinase B, gamma)". Hodgkinson CP, Sale EM, Sale GJ (2002). "Characterization of PDK2 activity against protein kinase B ... Walker KS, Deak M, Paterson A, Hudson K, Cohen P, Alessi DR (1998). "Activation of protein kinase B beta and gamma isoforms by ...
This protein kinase is calcium-independent and phospholipid-dependent. It is not activated by phorbol esters or diacylglycerol ... Phosphoinositide-dependent kinase-1, SMG1 (gene), Sequestosome 1, KRAS. Vimentin GRCh38: Ensembl release 89: ENSG00000163558 - ... This gene encodes a member of the protein kinase C (PKC) family of serine/threonine protein kinases. The PKC family comprises ... Lim YP, Low BC, Lim J, Wong ES, Guy GR (Jul 1999). "Association of atypical protein kinase C isotypes with the docker protein ...
... has been shown to interact with: AKT1, PKN2, PRKACA, PRKCD, PRKCI, Protein kinase Mζ, ... "Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and ... "Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/ ... "Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1". Science. 281 (5385): 2042-5 ...
"Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1". Science. 281 (5385): 2042-5 ... "Protein kinase M zeta synthesis from a brain mRNA encoding an independent protein kinase C zeta catalytic domain. Implications ... Protein kinase C, zeta (PKCζ), also known as PRKCZ, is a protein in humans that is encoded by the PRKCZ gene. The PRKCZ gene ... of the Caenorhabditis elegans UNC-76 protein involved in axonal outgrowth is a protein kinase C zeta-interacting protein". J. ...
OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proc. ... 1998). "Phosphoinositide-3- ... "Eosinophil granule cationic proteins: major basic protein is ... Eosinophil major basic protein, often shortened to major basic protein (MBP; also called Proteoglycan 2 (PRG2)) is encoded in ... Major basic protein has been shown to interact with Pregnancy-associated plasma protein A. Arylsulfatase GRCh38: Ensembl ...
... phosphoinositide-dependent kinase PDK1 and mammalian target of rapamycin mTORC2. It has been shown to "regulate several enzymes ... Serine/threonine-protein kinase Sgk1 also known as serum and glucocorticoid-regulated kinase 1 is an enzyme that in humans is ... This gene encodes a serine/threonine protein kinase that plays an important role in cellular stress response. This kinase ... "Thus SGK1 is either not a crucial element in the regulation of cell proliferation or apoptosis, or related kinase(s) can ...
... this phosphorylation is mediated by cAMP-dependent protein kinase A (PKA). Second allosteric regulation is mediated by binding ... "Small-molecule agonists of SHIP1 inhibit the phosphoinositide 3-kinase pathway in hematopoietic cells". Blood. 110 (6): 1942-9 ... by the cyclic AMP-dependent protein kinase". The Journal of Biological Chemistry. 284 (30): 20070-8. doi:10.1074/jbc. ... Leitges M, Gimborn K, Elis W, Kalesnikoff J, Hughes MR, Krystal G, Huber M (June 2002). "Protein kinase C-delta is a negative ...
The encoded protein is a general protein kinase capable of phosphorylating several known proteins. AKT2 has important roles in ... OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase". Proc. ... Delcommenne M, Tan C, Gray V, Rue L, Woodgett J, Dedhar S (1998). "Phosphoinositide-3- ... "Inhibition of insulin-induced activation of Akt by a kinase-deficient mutant of the epsilon isozyme of protein kinase C." J. ...
For example, MTag binds and activates Src-family protein tyrosine kinases in a PP2A-dependent manner, and in turn is ... phosphoinositide 3-kinase, and phospholipase Cγ1. The signaling functions of the phosphorylated MTag have been described as ... but has a number of protein-protein interaction sites that mediate interactions with proteins in the host cell. Particularly in ... The result of this genetic encoding is three proteins that share a common N-terminal sequence, forming a protein domain called ...
... is a lyso-sphingolipid protein kinase inhibitor. It has the molecular formula C18H39NO2 and is a colorless solid. ... Safingol can also inhibit phosphoinositide 3-kinase (PI3k), which is a critical component of the mTOR and MAPK/ERK pathways. ... This results in oxidative stress, leading to the generation of ROS that are both time and concentration-dependent. Together, ... Safingol competitively competes with phorbol dibutyrate at regulatory domains of the protein kinase C family, inhibiting the ...
... and a downstream target of this pathway is the protein kinase B (PKB) (Hodge et al., 2007). IL-6 activated PKB can ... It appears that unlike IL-6 signalling in macrophages, which is dependent upon activation of the NFκB signalling pathway, ... IL-6 activates the Phosphoinositide 3-kinase (PI3K) pathway, ... Protein superfamily[edit]. Interleukin is the main member of ... As IL-6 interacts with its receptor, it triggers the gp130 and IL-6R proteins to form a complex, thus activating the receptor. ...
If protein A is dependent on protein B for activation then the inhibition of either protein A or B will result in a cell losing ... in cell signaling proteins like protein tyrosine kinases and the growth factor receptor bound protein 2 (Grb2).[24]. * ... Pleckstrin homology domains bind to phosphoinositides and acid domains in signaling proteins.. *WW domain Main article: WW ... To test protein-protein interaction, the targeted protein cDNA and query protein cDNA were immobilized in a same coated slide. ...
Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... γ proteins.[17] Signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, sometimes ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... Whereas G proteins are activated by G protein-coupled receptors, they are inactivated by RGS proteins (for "Regulator of G ...
2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... Template Dependent Activity[edit]. TDT bound to three DNA strands demonstrating the active configuration of its template ... These include protein-protein interactions, like those with TdIF1. TdIF1 is another protein that interacts with TdT to inhibit ... "Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1804 (5): 1151-66. doi:10.1016/j.bbapap.2009.06.030. PMC 2846215 ...
CDC42, protein tyrosine kinase, phosphoinositide 3-kinase, and Src-family kinases then activate Arp2/3. This causes the ... Clathrin and Caveolin 2-Dependent Manner". Cellular Microbiology. 11 (4): 629-644. doi:10.1111/j.1462-5822.2008.01279.x. PMC ... This species of Rickettsia uses an abundant cell surface protein called OmpB to attach to a host cell membrane protein called ... Both rOmpA and rOmpB are members of a family of surface cell antigens (Sca) which are autotransporter proteins; they act as ...
DP2 and DP1 are G protein-coupled receptors, with the DP2 receptor coupled to Gi alpha subunit-dependent depression of cellular ... 15-deoxy-Δ12,14-PGJ2 forms an adduct with the IKK-β subunit of IκB kinase thereby inhibiting the kinases activity thereby ... 15-PGJ2 to inhibit the Phosphoinositide 3-kinase pathway of cell signaling. The direct injection of 15-d-Δ12,14-PGJ2 into the ... Akt and a p38 mitogen-activated protein kinases pathways to inhibit the actions of pro-inflammatory cytokines and/or the ...
The lipophilic diacylglycerol remains in the membrane, acting as a cofactor for the activation of protein kinase C. These ... They can also inhibit glutamate release and can modulate voltage-dependent calcium channels. Group I mGluRs, but not other ... Stimulating the receptors causes the associated enzyme phospholipase C to hydrolyze phosphoinositide phospholipids in the ... Proteins called PDZ proteins frequently anchor mGluRs near enough to NMDARs to modulate their activity. It has been suggested ...
The name Crk is from "CT10 Regulator of Kinase" where CT10 is the avian virus from which was isolated a protein, lacking kinase ... 1994). "Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src". Mol. Cell. Biol ... roles of phosphoinositide-3 kinase and protein kinase C". Blood. 95 (8): 2505-13. doi:10.1182/blood.V95.8.2505. PMID 10753828. ... related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins". ...
Activation of the ER complex causes increased kinase activity in phosphoinositide 3-kinases (PI3K) and mitogen-activated ... This is dependent upon the equilibrium of these 2 receptor types in target organs. These two ER types are encoded by different ... protein kinase (MAPK) as well as increases in concentrations of signaling molecules like calcium and nitric oxide. The main ... The anti-ER (SP1) antibody targets the ER alpha protein (ERα) located in the nucleus of ER positive normal and neoplastic cells ...
The protein encoded by this gene is a member of the homeodomain family of DNA binding proteins. It regulates gene expression, ... phosphoinositide 3-kinase (PI3K) which leads to tumor progression. Although CUX1 is mutated at a lower rate compared to other ... attachment region upstream of the T cell receptor beta gene enhancer binds Cux/CDP and SATB1 and modulates enhancer-dependent ... The human CASP protein is predicted to contain 678 amino acids, of which 400 are shared with CUTL1. CASP protein is ...
... as phosphoinositide-mediated endosomal sorting proteins. This BAR domain allows them to assembly in a dose-dependent manner a ... SNX8 acts as an adaptor or scaffolding protein by permitting the recruitment of the inhibitor of nuclear factor-kappa-B kinase ... are involved in protein-protein interactions. The SNX8 protein, even though is very similar to the other sorting nexins, ... The SNX-BAR proteins that contain both domains are a part of phosphoinositide-enriched, high-curvature tubular micro-domains of ...
"Assembly of a Fab1 phosphoinositide kinase signaling complex requires the Fig4 phosphoinositide phosphatase". Molecular Biology ... December 2008). "VAC14 nucleates a protein complex essential for the acute interconversion of PI3P and PI(3,5)P(2) in yeast and ... February 2019). "A family of PIKFYVE inhibitors with therapeutic potential against autophagy-dependent cancer cells disrupt ... "Entrez Gene: Phosphoinositide kinase, FYVE finger containing". Shisheva A, Sbrissa D, Ikonomov O (January 1999). "Cloning, ...
2003). "A sphingosine-dependent protein kinase that specifically phosphorylates 14-3-3 (SDK1) is identified as the kinase ... Phosphoinositide 3-kinase (PI3K) as an effector phosphorylates phosphatidylinositol bisphosphate (PIP2) to produce ... Sph is also known to interact with protein targets such as the protein kinase H homologue (PKH) and the yeast protein kinase ( ... 1997). "Kinase suppressor of Ras is ceramide-activated protein kinase". Cell. 89 (1): 63-72. doi:10.1016/S0092-8674(00)80183-X ...
Journal of Immunology, 2006 PMID 17056525 HIV Nef-mediated CD4 down-regulation is adaptor protein complex 2 dependent. Jin YJ, ... Journal of Immunology 2008 PMID 18523251 Prostaglandin E2 activates HPK1 kinase activity via a PKA-dependent pathway. ... and is prevented by an inhibitor of phosphoinositide 3-kinase activity. Slavik JM, Lim DG, Burakoff SJ, Hafler DA., Journal of ... protein oxidation and altered protein expression reveal targets of damage, stress response, and antioxidant responsiveness. ...
... protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by ... "Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves ... Lineage for Protein: Focal adhesion kinase 1 Q00944 "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". Guan JL, Shalloway D ( ... The encoded protein is a member of the FAK subfamily of protein tyrosine kinases that included PYK2, but lacks significant ...
The human dysferlin protein is a 237 kilodalton type-II transmembrane protein. It contains a large intracellular cytoplasmic N- ... FerA domain is a four helix bundle and it can interact with membrane, usually in a calcium-dependent manner. The most ... "Characterization of lipid binding specificities of dysferlin C2 domains reveals novel interactions with phosphoinositides". ... Dysferlin also known as dystrophy-associated fer-1-like protein is a protein that in humans is encoded by the DYSF gene. ...
Smudge cells are due to cancer cells lacking in vimentin, a type of cytoskeleton proteins which is a structural component in a ... While prognosis is highly variable and dependent on various factors including these mutations, the average 5-year relative ... Targeted drugs used in CLL include venetoclax (a Bcl-2 inhibitor), ibrutinib (a Bruton's tyrosine kinase inhibitor), idelalisib ... inhibitors of some forms of the enzyme phosphoinositide 3-kinase), as well as monoclonal antibodies against CD20 (rituximab, ...
PIP3 acts as a secondary messenger and induces the activation of phosphatidylinositol dependent protein kinase, which then ... The activated IRS-1 initiates the signal transduction pathway and binds to phosphoinositide 3-kinase (PI3K), in turn causing ... This protein then begins a phosphorylation cascade, culminating in the activation of mitogen-activated protein kinase (MAPK), ... This indirectly activates a protein kinase, PKB (Akt), via phosphorylation. PKB then phosphorylates several target proteins, ...
P binding protein of the WIPI (WD-repeat protein interacting with phosphoinositides) protein family, was recently shown to ... Chan EY (September 2012). "Regulation and function of uncoordinated-51 like kinase proteins". Antioxidants & Redox Signaling. ... This is directly related to the growth of cancer cells in a dose-dependent manner as well. These data support the development ... neurons gather ubiquitinated protein aggregates and degrade.[citation needed] Ubiquitinated proteins are proteins that have ...
PA acts as a signaling lipid, recruiting cytosolic proteins to appropriate membranes (e.g., sphingosine kinase 1). PA plays ... The curvature induced by these lipids was shown to be dependent not only on the structure of lysoPA versus PA but also on ... and phosphoinositides (PIP, PIP2, PIP3). PA concentrations are maintained at extremely low levels in the cell by the activity ... anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior". Proceedings of the National Academy of ...
"Mechanism of assembly of G protein betagamma subunits by protein kinase CK2-phosphorylated phosducin-like protein and the ... Ikeda SR (March 1996). "Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma subunits". Nature. 380 ... "Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation". Science. 287 (5455): 1049-53. Bibcode: ... Portal: Biology (Protein pages needing a picture, G proteins, Protein complexes). ...
... and enhance their selectivity toward certain G proteins. PIP2 has been shown to recruit G protein-coupled receptor kinase 2 ( ... Hay, Jesse C, Thomas M (1993). "Phosphatidylinositol transfer protein required for ATP-dependent priming of Ca2+-activated ... Rusten, Tor Erik; Stenmark, Harald (April 2006). "Analyzing phosphoinositides and their interacting proteins". Nature Methods. ... In this cascade, DAG remains on the cell membrane and activates the signal cascade by activating protein kinase C (PKC). PKC in ...
Caiati MD, Safiulina VF, Fattorini G, Sivakumaran S, Legname G, Cherubini E (February 2013). "PrPC controls via protein kinase ... although this was dependent on the soil type they were bound to. Proteins showing prion-type behavior are also found in some ... PrPC is readily digested by proteinase K and can be liberated from the cell surface in vitro by the enzyme phosphoinositide ... One idea, the "Protein X" hypothesis, is that an as-yet unidentified cellular protein (Protein X) enables the conversion of ...
"Blood cell counts and their correlation with creatine kinase and C-reactive protein in patients with acute myocardial ... and undergo selectin-dependent capture followed by integrin-dependent adhesion in most cases, after which they migrate into ... and the phosphoinositide 3-kinases (PI3Ks). In neutrophils, lipid products of PI3Ks regulate activation of Rac1, hematopoietic ... Neutrophils also release an assortment of proteins in three types of granules by a process called degranulation. The contents ...
ARG-binding protein 2γ, hepatitis B virus X protein, STE20-related kinase adaptor protein α, RhoI, Klotho, N-acetylglucosaminyl ... PAK1 has been shown to interact with: ARHGEF2, ARPC1B, BMX, C-Raf, CDC42, Cyclin-dependent kinase 5, DYNLL1, LIMK1, NCK1, ... phosphoinositides, ETK, AKT, JAK2, ERK, casein kinase II, Rac3, chemokine (C-X-C motif) ligand 1, breast cancer anti-estrogen ... However, IPA-3's pharmacokinetic properties as well as undesirable redox effects in cells, due to the continuous reduction of ...
It is a serine/threonine kinase that acts downstream of PIP3 and phosphoinositide-dependent kinase-1 in the PI3 kinase pathway ... Ribosomal protein S6 kinase beta-1 (S6K1), also known as p70S6 kinase (p70S6K, p70-S6K), is an enzyme (specifically, a protein ... The kinase activity of this protein leads to an increase in protein synthesis and cell proliferation. Amplification of the ... "Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases". Cell. 69 (7 ...
PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and ... We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth ... Filippa N, Sable CL, Hemmings BA, Van Obberghen E: Effect of phosphoinositide-dependent kinase 1 on protein kinase B ... Dutil EM, Toker A, Newton AC: Regulation of conventional protein kinase C isozymes by phosphoinositide-dependent kinase 1 (PDK- ...
... phosphorylate and activate most of these kinases, with the exception of Akt. We exploited this differential mechanism of ... The 3-phosphoinositide-dependent protein kinase 1 (PDK1) coordinates the PI 3-kinase signals by activating twenty three kinases ... The phosphoinositide 3-kinase (PI 3-kinase)/Akt signaling pathway plays essential roles during neuronal development. ... The phosphoinositide 3-kinase (PI 3-kinase)/Akt signaling pathway plays essential roles during neuronal development. The 3- ...
Phosphoinositide-dependent kinase-1 has been shown to interact with: AKT1, PKN2, PRKACA, PRKCD, PRKCI, Protein kinase Mζ, ... "Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and ... "Identification of regulatory phosphorylation sites in mitogen-activated protein kinase (MAPK)-activated protein kinase-1a/ ... "Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1". Science. 281 (5385): 2042-5 ...
Phosphoinositide Dependent Protein Kinase 1 Medicine and Dentistry 100% * Phosphoinositide-Dependent Kinase-1 Neuroscience 100% ... an Akt1 Kinase, is Involved in Dephosphorylation of Thr-308 of Akt1 in Chinese Hamster Ovary Cells. In: Journal of Biological ... an Akt1 Kinase, is Involved in Dephosphorylation of Thr-308 of Akt1 in Chinese Hamster Ovary Cells. Journal of Biological ... an Akt1 Kinase, is Involved in Dephosphorylation of Thr-308 of Akt1 in Chinese Hamster Ovary Cells. / Yamada, Tetsuya; Katagiri ...
Other proteins in same PDB: d1w1ga2. complexed with 4pt. has additional insertions and/or extensions that are not grouped ... Class b: All beta proteins [48724] (180 folds). *. Fold b.55: PH domain-like barrel [50728] (3 superfamilies). barrel, partly ... Protein 3-phosphoinositide dependent protein kinase-1 [117246] (1 species). *. Species Human (Homo sapiens) [TaxId:9606] [ ... Family b.55.1.1: Pleckstrin-homology domain (PH domain) [50730] (48 proteins). Pfam PF00169. ...
G-protein coupled receptor kinase 2 (beta-adrenergic receptor kinase 1) [50747] (2 species). ... Calcium-dependent activator protein for secretion, CAPS [117252] (1 species). *. Species Human (Homo sapiens) [TaxId:9606] [ ... Phosphoinositide phospholipase C, PLC-gamma-1 [141413] (1 species). contains split PH domain. ... Protein kinase c, d2 type [141419] (1 species). *. Species Human (Homo sapiens) [TaxId:9606] [141420] (1 PDB entry). Uniprot ...
... protein kinase B pathway which lead to enhanced adhesion, altered elasticity, and reduced motility of NSCLCs. Global gene ... B. pseudomallei cell lengths were strain-, drug- and drug concentration-dependent. CONCLUSIONS: Both resistant and susceptible ... signaling and a suppression of the phosphoinositide 3-kinases / ... protein targets, take formation, weight loss, rash burden, and ... Histidine-rich protein 2 (HRP2) detecting rapid diagnostic tests (RDTs) have played an important role in enabling prompt ...
GO:0006468 protein amino acid phosphorylation *GO:0004672 protein kinase activity *GO:0005524 ATP binding ... Protein prediction analysis (1) Protein prediction analysis (1) Prediction based on ESTScan [ Show ESTScan Detail] >SGN-P3266 ( ... Prot_kinase. Ser_thr_pkin_AS. 7. *i value: controls inflation, a process to dissipate family clusters. At high i value, genes ... This unigene is from an out-of-date build, Lycopersicon Combined #3. It has been split into SGN-U583884 and SGN-U583885 in the ...
... as a context-dependent modulator of immunity and inflammation. Recent advances in protein structure determination and drug ... This Review discusses the immunomodulatory properties of phosphoinositide 3-kinase-γ (PI3Kγ) in health and in the context of ... new insights have positioned phosphoinositide 3-kinase-γ (PI3Kγ) ... PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. ...
PI3K activates AKT, serum/glucocorticoid regulated kinase (SGK), phosphoinositide-dependent kinase 1 (PDK1), mammalian target ... PI3K is a major signaling hub downstream of human epidermal growth factor receptor (HER)2 and other receptor tyrosine kinases. ... In estrogen receptor (ER)+ breast cancer cells, PI3K activation promotes estrogen-dependent and -independent ER transcriptional ... Mutations in genes that constitute the phosphatidylinositol 3-kinase (PI3K) pathway occur in >70% of breast cancers. ...
JavaScript is disabled for your browser. Some features of this site may not work without it ...
Misregulation of the PI3 kinase pathway is one of the most familiar events in GBM. While the PI3 kinase signalling regulated ... Taken together, our study uncovered the PI3 kinase regulated miRNome in GBM. miR-326, a PI3 kinase pathway inhibited miRNA, was ... The objective of this study was to elucidate the PI3 kinase pathway regulated miRNAs in GBM. miRNA expression profiling was ... We identified several miRNA that were regulated by PI3 kinase pathway. miR-326, a GBM downregulated miRNA, was validated as one ...
... showed overexpression of active protein enzyme Akt1 caused murine β cells to grow larger and produce more insulin - an effect ... The 3-phosphoinositide-dependent protein kinase Akt is a signaling molecule that mediates the actions of insulin and insulin- ...
... kinase in small cell lung cancer cells mediates anchorage-independent proliferation via a protein kinase B and p70s6k-dependent ... Membrane-associated Akt is activated by Ser473 phosphorylation by membrane-associated phosphoinositide-dependent kinase-1 (3) ... The protein kinase family has ,800 human members (11) among which receptor protein tyrosine kinases are frequently targets for ... activation of signaling pathways that include the Ras/mitogen-activated protein kinase kinase/mitogen-activated protein kinase ...
cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4). 2. 2. CEBPA. 88. CCAAT/enhancer binding protein (C/EBP), alpha. 14. ... phosphoinositide-3-kinase, regulatory subunit 1 (alpha). 16. 65. PIN1. 62. peptidylprolyl cis/trans isomerase, NIMA-interacting ... low density lipoprotein receptor-related protein 2. 2. 8. MAP3K5. 179. mitogen-activated protein kinase kinase kinase 5. 4. 29 ... serine/threonine kinase 11. 5. 18. STUB1. 245. STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase. 1. ...
... protein kinase B pathway which lead to enhanced adhesion, altered elasticity, and reduced motility of NSCLCs. Global gene ... expression analysis identified dose-dependent changes to nuclear factor kappa-light-chain-enhancer, epithelial tumor, and ... decrease in matrix metalloproteinases expression via altered focal adhesion signaling and a suppression of the phosphoinositide ... followed by both single point and real-time assays to evaluate changes in cellular gene and protein expression, adhesion, ...
GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK ... by the insulin receptor tyrosine kinase (INSR). This allows association of IRSs with the regulatory subunit of phosphoinositide ... Akt also leads to mTOR-mediated activation of protein synthesis by eIF4 and p70S6K. The translocation of GLUT4 protein is also ... a serine kinase. Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) ...
... of P2Y2 receptor induces c-FOS protein through a pathway involving mitogen-activated protein kinases and phosphoinositide 3- ... of P2Y2 receptor induces c-FOS protein through a pathway involving mitogen-activated protein kinases and phosphoinositide 3- ... 1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione 38% ...
3phosphoinositide-dependent kinase-1 is essential for ischemic preconditioning of the myocardium. Budas, G. R., Sukhodub, A., ... conformational analysis and stereoselective recognition by the VHL E3 ubiquitin ligase for targeted protein degradation. Testa ... structural and functional homology with the Drosophila DSTPK61 kinase. Alessi, D. R., Deak, M., Casamayor, A., Caudwell, F. B. ... Wang, J., Xiao, X., Huang, Z. & Melzer, A., Jul 2019, In: Procedia Manufacturing. 30, p. 3-10 8 p.. Research output: ...
3D visualization and cluster analysis of unstructured protein sequences using ARCSA with a file conversion approach. Vignesh, U ... 3-vertex full balance index set of graphs. Devadas, N. C., Gowtham, H. J., Dsouza, S. & Bhat, P. G., 2020, In: Advances in ... 3-(2,4-Dichloro-phen-yl)-5-methyl-1,2,4-oxadiazole. Fun, H. K., Rosli, M. M., Rai, S., Isloor, A. M. & Shetty, P., 28-04-2010, ... 3-(2,4-Dichloro-phen-yl)-5-phenyl-1,2,4-oxadiazole. Fun, H. K., Rosli, M. M., Rai, S., Isloor, A. M. & Shetty, P., 28-04-2010, ...
... protein synthesis and inhibition of pro-apoptotic proteins [1-4]. Dysregulation of AKT-dependent pathways is associated with ... or small Ras-related GTPases that turn on class I PI3K kinases driving the synthesis of the phosphoinositide second messenger ... Resistance of Akt kinases to dephosphorylation through ATP-dependent conformational plasticity. . Proc. Natl. Acad. Sci. U.S.A. ... In addition to the well-documented kinase-dependent functions of AKT, there is evidence that AKT can regulate some cellular ...
Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle ... Effects of high-fat diet and AMP-activated protein kinase modulation on the regulation of whole-body lipid metabolism. J Lipid ... D) Protein expression of AKT2, E) TBC1D4, F) GLUT4, and G) Hexokinases II (n=16-18). H) Representative phospho-blots. I) ... Total proteins and phosphorylation levels of relevant proteins were determined by standard immunoblotting techniques loading ...
Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation.. Biondi RM. Trends Biochem Sci 2004 Mar; 29 (3 ... and cGMP-dependent protein kinases (PKA and PKG), the protein kinase C family (PKC), PKB/Akt, ribosomal protein S6 kinases, and ... Regulation of the interaction between protein kinase C-related protein kinase 2 (PRK2) and its upstream kinase, 3- ... phosphoinositide-dependent protein kinase 1 (PDK1).. Dettori R, Sonzogni S, Meyer L, Lopez-Garcia LA, Morrice NA, Zeuzem S, ...
General protein information Go to the top of the page Help Preferred Names. DNA damage-regulated autophagy modulator protein 1 ... Title: p53-Dependent PUMA to DRAM antagonistic interplay as a key molecular switch in cell-fate decision in normal/high glucose ... DRAM1 regulates autophagy and cell proliferation via inhibition of the phosphoinositide 3-kinase-Akt-mTOR-ribosomal protein S6 ... mRNA and Protein(s) * XM_005269004.3 → XP_005269061.1 DNA damage-regulated autophagy modulator protein 1 isoform X1 ...
DNA Dependent Protein Kinase 100% * Phosphoinositide 3-Kinase 71% * Chemotherapy 57% * Glioblastoma 57% ... Evaluation of protein kinase inhibitors with plk4 cross-over potential in a pre-clinical model of cancer. Suri, A., Bailey, A. ... Polo-like kinase 4 (PLK4) is overexpressed in central nervous system neuroblastoma (CNS-NB). Bailey, A. W., Suri, A., Chou, P. ... Inhibition of polo-like kinase 4 (PLK4): A new therapeutic option for rhabdoid tumors and pediatric medulloblastoma. Sredni, S ...
... which promote phosphoinositide-dependent kinase-1-mediated phosphorylation, activating Akt (35). Akt has two phosphorylation ... Akt is a serine/threonine protein kinase and downstream target of PI3K (34). Under the action of insulin, PI3K activation ... Role of TRB3 in inhibition of Akt/protein kinase B activation. J Biol Chem. 281:11126-11134. 2006. View Article : Google ... The α subunit is responsible for binding insulin, whilst the β subunit has intrinsic tyrosine protein kinase (TPK) activity ...
... which in turn activates ATM kinase to gain survival advantages, through Akt. ... Ataxia telangiectasia mutated (ATM), ATM- and Rad3-related protein (ATR) and DNA-dependent protein kinase catalytic subunit ( ... are three drivers of DDR which belong to the family of phosphoinositide 3-kinase like kinases (PIKKs). PIKKs respond to the DNA ... 2005) Deficiency in the catalytic subunit of DNA-dependent protein kinase causes down-regulation of ATM Cancer Research 65:1670 ...
In eukaryotes, AGC kinase family proteins are regulated by 3-phosphoinositide-dependent protein kinase 1 (Pdk1). In Arabidopsis ... In eukaryotes, AGC kinase family proteins are regulated by 3-phosphoinositide-dependent protein kinase 1 (Pdk1). In Arabidopsis ... In eukaryotes, AGC kinase family proteins are regulated by 3-phosphoinositide-dependent protein kinase 1 (Pdk1). In Arabidopsis ... In eukaryotes, AGC kinase family proteins are regulated by 3-phosphoinositide-dependent protein kinase 1 (Pdk1). In Arabidopsis ...
Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3- ... Cell biology depends on the interactions of macromolecules, such as protein-DNA, protein-protein or protein-nucleotide ... Many of the actions of receptor tyrosine kinases are mediated by the protein Ras, including the activation of various ... Click on the protein counts, or double click on taxonomic names to display all proteins containing RasGEF domain in the ...
Cytoskeletal reorganization by G protein-coupled receptors is dependent on phosphoinositide 3-kinase γ, a Rac guanosine ... receptor tyrosine kinases, G protein-coupled receptors, and other transmembrane proteins (Quilliam et al., 2002). Signaling ... Cytoskeletal reorganization by G protein-coupled receptors is dependent on phosphoinositide 3-kinase γ, a Rac guanosine ... Phosphorylation-dependent and constitutive activation of Rho proteins by wild-type and oncogenic Vav-2. EMBO J. ...
  • In the present investigation, we show that expression of PDK1 strongly induced ECM invasion, MT1-MMP levels and MMP-2 activity in mammary epithelial cells that was dependent on PI3K activation. (biomedcentral.com)
  • PDPK1 functions downstream of PI3K through PDPK1's interaction with membrane phospholipids including phosphatidylinositols, phosphatidylinositol (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. (wikipedia.org)
  • PI3K indirectly regulates PDPK1 by phosphorylating phosphatidylinositols which in turn generates phosphatidylinositol (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate. (wikipedia.org)
  • Over the past two decades, new insights have positioned phosphoinositide 3-kinase-γ (PI3Kγ) as a context-dependent modulator of immunity and inflammation. (nature.com)
  • Recent advances in protein structure determination and drug development have allowed for generation of highly specific PI3Kγ inhibitors, with the first now in clinical trials for several oncology indications. (nature.com)
  • Fig. 1: Context-dependent signalling of PI3Kγ complexes. (nature.com)
  • Fig. 3: Involvement of PI3Kγ and PI3Kβ in progression of atherosclerosis. (nature.com)
  • AKT is a family of serine/threonine kinases consisting of three isoforms (AKT1, AKT2 and AKT3), regulated upstream by the activation of phosphatidylinositol 3-kinases (PI3K) following growth factor stimulation. (portlandpress.com)
  • The insulin receptor (InsR)/insulin receptor substrate (IRS)/phosphoinositide 3-kinase (PI3K)/Akt pathway is the critical homeostatic cascade linking insulin release to tissue glucose uptake ( 7 ). (spandidos-publications.com)
  • A central regulatory mechanism of FOXO proteins is phosphorylation by the serine-threonine kinase Akt/protein kinase B (Akt/PKB), downstream of phosphatidylinositol 3-kinase (PI3K), in response to insulin or several growth factors. (genome.jp)
  • Our previous results revealed a new pathway in which amino acids permit insulin-induced activation of the protein kinase B (PKB)/mTOR pathway in freshly isolated adipocytes when phosphatidylinositol 3-kinase (PI3K) is inhibited. (c3m-nice.fr)
  • Furthermore, PFIO decreased the phosphorylation levels of mitogen-activated protein kinases (MAPKs) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) as well as the expression level of COX-2, and inhibited the nuclear translocation of nuclear factor κB (NF-κB) in A549 cells. (spandidos-publications.com)
  • The expression of MMP genes is primarily regulated through transcriptional factors such as activator protein-1 (AP-1) and/or nuclear factor κB (NF-κB) via mitogen-activated protein kinases (MAPKs) or phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathways ( 10 - 12 ). (spandidos-publications.com)
  • The class IA phosphatidylinositol 3-kinases (PI3K) is involved in controlling changes in cell morphology, which is a highly coordinated cellular event. (omicsdi.org)
  • Here, we tested the hypothesis that phosphoinositide 3-kinase (PI3K) inhibitors may rescue the endocytic defect imparted by OCRL loss, by rebalancing phosphoinositide signals to the actin machinery. (omicsdi.org)
  • Levels of PI 3,4,5-trisphosphate, PI(4,5)P2 and PI(3)P were all reduced with alpelisib treatment, and siRNA knockdown of the PI3K catalytic subunit p110? (omicsdi.org)
  • Genetic alterations in PI3K (phosphoinositide 3-kinase) signalling are common in cancer and include deletions in PTEN (phosphatase and tensin homologue deleted on chromosome 10), amplifications of PIK3CA and mutations in two distinct regions of the PIK3CA gene. (omicsdi.org)
  • The p85 subunit of phosphoinositide 3-kinase ( PI3K ), bound to phosphorylated IRS, activates the catalytic subunit p110 . (bio-rad-antibodies.com)
  • Phosphorylation of PI3K phosphatidylinositol-4, 5-bisphophaste (PIP2) by PI3K to phosphatidylinositol-3, 4, 5-trisphophaste (PIP3), activates 3-phosphoinositide dependent protein kinase-1 ( PDK1 ). (bio-rad-antibodies.com)
  • The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). (umbc.edu)
  • It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. (umbc.edu)
  • Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide-dependent protein kinase (PDK1)-protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight molecules that can potentially be targeted therapeutically. (novartis.com)
  • EGFR-dependent breast cancer cell lines undergo a striking reversion of the malignant phenotype upon treatment with inhibitors targeting the receptor, or downstream signalling intermediates such as mitogen-activated protein kinase and PI3K (phosphoinositide 3-kinase). (elsevier.com)
  • Activation of pi3k leads to activation of phosphoinositide-dependent kinases (pdks) 1 and 2, which activate multiple protein kinases, including akt/protein. (roblesdance.shop)
  • The action of phosphatidylinositol 3-kinase (pi3k), a downstream kinase activated by receptor tyrosine kinases, produces a series of phosphorylated. (roblesdance.shop)
  • We detected increased amount of p-tau and α-synuclein proteins, altered phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) and mitogen-activated protein kinase (MAPK) signaling pathways, and deregulation of cyclin-dependent kinase 5 ( Cdk5). (extremalby.com)
  • The protein encoded by PIK3C2A gene belongs to the phosphoinositide 3-kinase (PI3K) family. (bio-rad-antibodies.com)
  • Interpreting the info by a powerful style of the network, it had been argued that mTORC2 activation Oxaliplatin (Eloxatin) IC50 pathway may result from the IR or the insulin receptor substrate-1 (IRS1), perhaps with a variant from the Oxaliplatin (Eloxatin) IC50 phosphatidylinositol 3-kinase (PI3K) [10]. (gasyblog.com)
  • BACKGROUND: Owing to its role in cancer, the phosphoinositide 3-kinase (PI3K)/Akt pathway is an attractive target for therapeutic intervention. (bath.ac.uk)
  • Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling. (cansar.ai)
  • In der Strahlentherapie spielt neben der Existenz von TSZ auch die strahlenindu-zierte Aktivierung des Epidermalen Wachstumsfaktorrezeptors (EGFR) und seinen downstream Signalkaskaden, wie z.B. dem Phosphoinositid-3 Kinase (PI3K)/Akt Signalweg, dem mitogen-activated protein kinase (MAPK) Signalweg und dem JAK/STAT Signalweg eine wichtige Rolle. (uni-hohenheim.de)
  • Further, experimental validation showed that the QX1 formula inhibited the activity of calcium/calmodulin-dependent protein kinase II (CaMKII), MAPK (P38, ERK1/2, and JNK), and TLR4/NF- κ B signaling pathways but promoted the activation of the PI3K/AKT pathway. (hindawi.com)
  • Background Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. (researchsquare.com)
  • The phosphatidylinositol 3-kinase (PI3K) / Akt / mammalian target of rapamycin (mTOR) signaling axis plays an important physiologic role in protein synthesis, gene transcription, cell growth and apoptosis. (researchsquare.com)
  • In acute leukemias PI3K/Akt signaling activity was demonstrated to be correlated with an inferior prognosis via contribution to proliferation, survival and drug resistance in acute myeloid leukemia 3,10-12 , in T-cell acute lymphoblastic leukemia (T-ALL) 13 and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). (researchsquare.com)
  • 14,15,16 Herein in Philadelphia chromosome positive (Ph+) BCP-ALL PI3K signaling has been shown to be involved in mutation-independent resistance to ABL-directed tyrosine kinase inhibitors 14 and recent preclinical data also suggest a role in Philadelphia chromosome negative (Ph-) BCP-ALL. (researchsquare.com)
  • While mutations of the PI3KCA gene are rare in leukemia, events upstream of PI3K are commonly implicated in causing aberrant activation of this pathway, e.g. activating mutations of the receptor tyrosine kinases (RTKs), Fms-like tyrosine kinase 3 ( FLT3 ) and KIT receptor tyrosine kinase, BCR-ABL1 fusion gene, or activating mutations in NRas and KRas . (researchsquare.com)
  • PITPα-mediated axonal outgrowth is sensitive to phosphoinositide 3-kinase (PI3K) inhibition and shows dependency on the Akt/GSK-3/CRMP-2 pathway. (silverchair.com)
  • We conclude that PITPα controls the polarized extension of axonal processes through the provision of PtdIns for localized PI3K-dependent signalling. (silverchair.com)
  • These diets slow cancer by inhibiting insulin/IGF and downstream intracellular signaling pathways, such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR). (ketotrakmeter.com)
  • AKT is a key player in the phosphoinositide 3-kinase (PI3K)-AKT signalling pathway. (bmj.com)
  • Activated PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP2) at the plasma membrane to phosphatidylinositol (3,4,5)-triphosphate (PIP3). (bmj.com)
  • An important target of Gβγ is phosphoinositide 3 kinase γ (PI3Kγ), a major isoform of PI3K whose receptor-dependent activation relies primarily on the Gβγ subunit. (acrabstracts.org)
  • Phosphoinositide 3-kinase (PI3K) inhibitor (LY 294002) also clogged phorbol 12-myristate 13-acetate (PMA)Cinduced down-regulation of LRP. (globaltechbiz.com)
  • 6976, bisindolylmaleimide, mitogen-activated proteins (MAP)/ERK kinase (MEK) inhibitor (UO 126), PEA, and PI3K inhibitor "type":"entrez-nucleotide","attrs":"text message":"LY294002″,"term_id":"1257998346″,"term_text message":"LY294002″LY294002 are items of Calbiochem. (globaltechbiz.com)
  • The epidermal growth factor (EGF) activates the phosphatidylinositol 3-kinase (PI3K)-Akt cascade among additional signaling pathways. (rmrfotoarts.com)
  • PI3K is a family of phospholipid kinase that is divided into three classes based on structure, function and substrate specificity. (biomedcentral.com)
  • The P-Rexes are functionally unique in that they require simultaneous signals from PhosphoInositide-3-Kinase (PI3K) and G-protein coupled-receptor (GPCR) pathways for their activation. (biomedcentral.com)
  • Phosphoinositide 3-kinase (PI3K) has been shown previously to be essential for eosinophil chemotactic responses to some stimuli but not others. (keele.ac.uk)
  • Human blood neutrophils have been shown to utilize two antagonistic signalling pathways for chemotaxis: PI3K and p38 mitogen-activated protein kinase (p38 MAPK). (keele.ac.uk)
  • The complementary pattern of inhibition observed in the present study provides evidence that distinct PI3K-dependent and p38 MAPK-dependent chemoattractants may also exist for eosinophils. (keele.ac.uk)
  • Activation of phosphoinositide 3-kinase (PI3K) is a critical step in signal transduction pathways triggered by a variety of extracellular stimuli. (uci.edu)
  • The lipid products of PI3K serve as second messengers to recruit specific phospholipid-binding proteins to the plasma membrane. (uci.edu)
  • Many isoforms of PI3K are expressed in mammalian cells, and many putative effector proteins have been identified. (uci.edu)
  • One crucial protein kinase downstream of PI3K is the mammalian target of rapamycin (mTOR). (uci.edu)
  • Only PI3K inhibitor, but not kinase inhibitors for MEK, ERK1/2, p38 MAPK, JNK, protein kinase C, and protein kinase A, completely abolished this tumor cell contact-associated protection and in parallel restored Fas-induced Bcl-x L cleavage as well as decreasing the phosphorylation of Bad at serine 136. (aai.org)
  • He provided seminal contributions in the characterization of phosphoinositide 3-kinases (PI3K) as drug targets in cancer and inflammation. (lifeboat.com)
  • He produced the first knockout mice for a PI3K catalytic subunit and demonstrated the role of PI3Kgamma in chemotaxis of leukocytes in Negative feedback regulation of Rac in leukocytes from mice expressing a constitutively active phosphatidylinositol 3-kinase γ . (lifeboat.com)
  • Knockdown of the tumor suppressor phosphatase Phosphatase and tensin homologue deleted on chromosome 10 ( PTEN ) with shRNA in three estrogen receptor (ER)-positive breast cancer cell lines resulted in increased phosphatidylinositol-3 kinase (PI3K) and AKT activities, resistance to tamoxifen and fulvestrant, and hormone-independent growth. (aacrjournals.org)
  • Importantly, mechanically induced Yki nuclear localisation also requires nutritionally induced insulin/insulin-like growth factor 1 (IGF-1) signalling (IIS) via phosphatidyl inositol-3-kinase (PI3K), phosphoinositide-dependent kinase 1 (PDK1 or PDPK1), and protein kinase B (Akt or PKB) in the follicular epithelium. (figshare.com)
  • [ 2 ] While activating ESR1 mutations have emerged as a key mechanism in resistance to AIs (but not to fulvestrant), [ 5 ] adaptive signalling via the mammalian target of rapamycin (mTOR)/phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway also plays an important role. (medscape.com)
  • The phosphatidylinositol 3-kinase (PI3K) signaling pathway has emerged as a major regulator of cellular functions and has been implicated in several pathologies involving remodeling of extracellular matrix ( ECM). (uws.ac.uk)
  • Phosphatidylinositol 3'-kinase (PI3K)/Akt is a common signaling pathway for oncogenes and tumor suppressor genes and is involved in VEGF regulation. (ox.ac.uk)
  • The phosphoinositide 3-kinase (PI 3-kinase)/Akt signaling pathway plays essential roles during neuronal development. (uab.cat)
  • An important mechanism for increased cell survival in many cancers is mediated by the phosphatidylinositol-3-kinase (PI3-K)/Akt (protein kinase B) signaling pathway that is activated by receptor and oncogenic protein tyrosine kinases ( 2 ). (aacrjournals.org)
  • In yeast, Pil1 and Lsp1 are regulated by a pair of redundant protein kinases Pkh1 and Pkh2 mediating the long-chain-base-signaling pathway. (biomedcentral.com)
  • BioVision proudly offers an array of STAT inhibitors either directly acting on STAT proteins or other proteins playing critical roles in the STAT signaling pathway. (biovision.com)
  • AKT, a phospholipid-binding serine/threonine kinase, is a key component of the phosphoinositide 3-kinase cell survival signaling pathway that is aberrantly activated in many human cancers. (uthscsa.edu)
  • This kinase is activated by Rho family of small G proteins and may mediate the Rho-dependent signaling pathway. (innatedb.com)
  • Activation of cytosolic phosphoinositide-3 kinase (PI-3K) signaling pathway has been well established to regulate gene expression, cell cycle, and survival by feeding signals to the nucleus. (uky.edu)
  • Components of the PI-3K signaling pathway, including PI3-kinase and its downstream kinase Akt, have been identified at the nuclear level. (uky.edu)
  • Consistent with the presence of a complete PI-3K signaling pathway in the nucleus, we have recently found that phosphoinositide-dependent kinase 1 (PDK1), a kinase functioning downstream of PI-3K and upstream of Akt, is a nucleo-cytoplasmic shuttling protein. (uky.edu)
  • Induction of mitogen-activated protein kinase phosphatase 1 by the stress-activated protein kinase signaling pathway but not by extracellular signal-regulated kinase in fibroblasts. (ucdenver.edu)
  • Inhibition of a signaling pathway in cardiac muscle cells by active mitogen-activated protein kinase kinase. (ucdenver.edu)
  • Reuveny, M., Heller, H., and Bengal, E . (2004) RhoA controls myoblast survival by inducing the phosphatidylinositol 3-kinase-Akt signaling pathway . (technion.ac.il)
  • Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-1alpha, HIF-2alpha, and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway. (ox.ac.uk)
  • Phosphorylation of a conserved docking site in the substrate is a requisite for PDK1 to recognize, phosphorylate and activate most of these kinases, with the exception of Akt. (uab.cat)
  • Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP. (systemsbiology.net)
  • This reaction requires the binding of a regulatory cyclin subunit and full activity requires stimulatory phosphorylation by a CDK-activating kinase (CAK). (systemsbiology.net)
  • Phosphorylation at three conserved residues results in the export of FOXO proteins from the nucleus to the cytoplasm, thereby decreasing expression of FOXO target genes. (genome.jp)
  • 2-O-Bn-InsP(5) specifically inhibits 3-phosphoinositide-dependent protein kinase 1 (PDK1) in vitro (IC50 in the low nanomolar range) and the PDK1-dependent phosphorylation of Akt in cell lines and excised tumours. (bath.ac.uk)
  • In vivo regulation of phosphoinositide 3-kinase in retina through light-induced tyrosine phosphorylation of the insulin receptor beta-subunit. (ouhsc.edu)
  • G-protein-coupled receptor rhodopsin regulates the phosphorylation of retinal insulin receptor. (ouhsc.edu)
  • Light-induced tyrosine phosphorylation of rod outer segment membrane proteins regulate the translocation, membrane binding and activation of type II a phosphatidylinositol-5-phosphate 4-kinase. (ouhsc.edu)
  • Spatial and temporal aspects and the interplay of Grb14 and protein tyrosine phosphatase-1B on the insulin receptor phosphorylation. (ouhsc.edu)
  • A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. (jefferson.edu)
  • This then recruits AKT to phosphoinositide dependent kinase 1 (PDK1) and mechanistic target of rapamycin complex 2 (mTORC2) to activate AKT via phosphorylation at two residues, Thr308 and Ser473. (bmj.com)
  • of PDK1 a kinase involved in Akt phosphorylation at Thr308 was not reduced in transgenic mice. (rmrfotoarts.com)
  • Results expressed as the relationship between phosphorylation and protein content of Akt demonstrated that even while Akt phosphorylation was induced by EGF in the transgenic mice Akt response to this growth factor TNFSF8 was lower in these animals (Fig. 1A). (rmrfotoarts.com)
  • Moreover when phosphorylation levels were related to the protein content phosphorylation at this residue was found to be not significantly induced by GH or EGF in the liver of transgenic mice (Fig. 1A). (rmrfotoarts.com)
  • It is well established that the Ser/Thr kinase phosphoinositide-dependent kinase 1 (PDK1) governs phosphorylation of Thr308 while the enzyme that mediates phosphorylation at Ser473 remains controversial. (rmrfotoarts.com)
  • Moreover, the kinase activity of DNA-PKcs was inhibited by anti-DPK3-scFv, which was displayed by the decreased phosphorylation levels of its target Akt/S473 and the autophosphorylation of DNA-PKcs on S2056 induced by radiation. (biomedcentral.com)
  • Furthermore, an extensive interplay between O -GlcNAc modification and serine/threonine phosphorylation in a variety of proteins has been reported to exist. (biomedcentral.com)
  • However, our understanding of the regulatory mechanisms involved in O -GlcNAc modification and its interplay with serine/threonine phosphorylation in proteins is still elusive. (biomedcentral.com)
  • Recent success in the mapping of O -GlcNAc modification sites in proteins as a result of technological advancement in mass spectrometry have revealed two important clues which may be inherently connected to the regulation of O -GlcNAc modification and its interplay with phosphorylation in proteins. (biomedcentral.com)
  • Second, the prevalence of tyrosine phosphorylation among O -GlcNAc modified proteins is exceptionally higher (~68%) than its normal occurrence (~2%) alone. (biomedcentral.com)
  • We hypothesize that phosphorylation may be a requisite for O -GlcNAc modification and tyrosine phosphorylation plays a role in the interplay between O -GlcNAc modification and serine/threonine phosphorylation in proteins. (biomedcentral.com)
  • Our hypothesis provides an opportunity to understand the underlying mechanism involved in O -GlcNAc modification and its interplay with serine/threonine phosphorylation in proteins. (biomedcentral.com)
  • O -GlcNAc cycling in proteins, mediated by the enzymes O -GlcNAc transferase (OGT) and O -GlcNAc amidase (OGA), is dynamically regulated in response to various stimuli and is remarkably similar to phosphorylation [ 1 ]. (biomedcentral.com)
  • As O -GlcNAc modification in protein occurs at serine/threonine residues, the potential for interplay between serine/threonine phosphorylation and O -GlcNAc modification has been realized very early on [ 4 ]. (biomedcentral.com)
  • However, unlike phosphorylation which is regulated by hundreds of kinases and phosphatases, O -GlcNAc cycling has only two mediators: OGT and OGA [ 1 ]. (biomedcentral.com)
  • This would imply that there must be fundamental differences in the way O -GlcNAc modification in proteins is regulated in relation to phosphorylation. (biomedcentral.com)
  • Furthermore, we downregulated ATR applying siRNA in HEK293 cells to figure out no matter whether etoposide induction of both mTOR protein and phosphorylation at Ser2481 had been dependent on ATR (Figure 2B). (5htreceptor.com)
  • To ensure that ATR siRNA had sufficiently suppressed ATR activity, phosphorylation of Chk1 (Ser345), a well-known substrate of ATR, was monitored by western blot (Figure 2B).Taken collectively, our outcomes show that etoposide-induced boost in mTOR is independent of p53, but dependent on ATM and ATR activity. (5htreceptor.com)
  • It contains multiple Tyr phosphorylation motifs that serve as docking sites for SH2 domain-containing proteins, like the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3-K), growth factor receptor binding protein-2 (Grb2), Nck, Crk, Fyn, SHP-2, and others, all of which mediate the metabolic and growth-promoting functions of insulin ( 2 , 17 ). (diabetesjournals.org)
  • Regulates ribosome synthesis by activating RNA polymerase III-dependent transcription through phosphorylation and inhibition of MAF1 a RNA polymerase III-repressor. (ucsc.edu)
  • mTORC1 exerts a feedback control on upstream growth factor signaling that includes phosphorylation and activation of GRB10 a INSR-dependent signaling suppressor. (ucsc.edu)
  • Plays a critical role in the phosphorylation at 'Ser-473' of AKT1, a pro- survival effector of phosphoinositide 3-kinase, facilitating its activation by PDK1. (ucsc.edu)
  • Activation of mTORC1 by growth factors such as insulin involves AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase a potent activator of the protein kinase activity of mTORC1. (ucsc.edu)
  • Insulin-stimulated and amino acid-dependent phosphorylation at Ser-1261 promotes autophosphorylation and the activation of mTORC1. (ucsc.edu)
  • Growth factor-stimulated phosphorylation cascades: activation of growth factor-stimulated MAP kinase. (ucdenver.edu)
  • Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity. (ucdenver.edu)
  • Extracellular signal-regulated kinase activates topoisomerase IIalpha through a mechanism independent of phosphorylation. (ucdenver.edu)
  • Mitogen-activated protein (MAP) kinase phosphorylation of MAP kinase kinase: determination of phosphorylation sites by mass spectrometry and site-directed mutagenesis. (ucdenver.edu)
  • Determination of v-Mos-catalyzed phosphorylation sites and autophosphorylation sites on MAP kinase kinase by ESI/MS. (ucdenver.edu)
  • They are also involved in the regulation of tau phosphorylation and amyloid precursor protein (APP) processing. (bmj.com)
  • Phosphorylation at three conserved sites in the kinase domain is required for catalytic activity. (bdbiosciences.com)
  • We verified that Arbidol is a potential ataxia telangiectasia and Rad3-related (ATR) inhibitor via binding to ATR kinase to reduce the phosphorylation and activation of minichromosome maintenance protein 2 at Ser108. (elifesciences.org)
  • Through the phosphorylation of downstream kinases, like Akt, PDK1 has been shown to be involved in several different cell functions, such as protein synthesis, cell survival, glucose metabolism, and cell adhesion and migration. (ecmbio.com)
  • We now present evidence showing that PDK1-expressing cells exhibit enhanced anchorage-dependent and -independent cell growth and are highly invasive when grown on Matrigel. (biomedcentral.com)
  • PDK1 mediates its effect in part by MT1-MMP induction, which in turn activates MMP-2 and modulates the ECM proteins decorin and collagen. (biomedcentral.com)
  • The 3-phosphoinositide-dependent protein kinase 1 (PDK1) coordinates the PI 3-kinase signals by activating twenty three kinases of the AGC family including Akt. (uab.cat)
  • PDK1 activates Akt by phosphorylating Thr 308 in Akt's kinase domain. (guidetomalariapharmacology.org)
  • Serine/Threonine Kinases (STKs), Phosphoinositide-dependent kinase 1 (PDK1) subfamily, catalytic (c) domain. (umbc.edu)
  • PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. (umbc.edu)
  • The 3-phosphoinositide dependent protein kinase-1 (PDPK1/PDK1) is reported to phosphorylate this kinase, which may mediate insulin signals to the actin cytoskeleton. (innatedb.com)
  • Akt is certainly phosphorylated on Thr308 with the phosphoinositide-dependent proteins kinase-1 (PDK1) and on Ser473 by mTORC2 [4], as well as the maximal Akt activity is certainly attained when the molecule is certainly phosphorylated on both residues, enabling the translocation from the insulin-regulated blood sugar transporters (GLUT4) in muscle tissue and adipose tissues [5,6]. (gasyblog.com)
  • PDK1 and mTORC2 also react to the activation from the insulin-like development aspect 1 (IGF1) [3]. (gasyblog.com)
  • New"-clear functions of PDK1: Beyond a master kinase in the cytosol? (uky.edu)
  • We also summarize some of the kinase-independent activities of PDK1 in cell signaling. (uky.edu)
  • Dive into the research topics of '"New"-clear functions of PDK1: Beyond a master kinase in the cytosol? (uky.edu)
  • Regulation of EAAT3 activity involves a signaling cascade including the phosphatidylinositol-3 (PI3)-kinase, the phosphoinositide dependent kinase PDK1, and the serum and glucocorticoid inducible kinase SGK1. (elsevier.com)
  • 3-Phosphoinositide-dependent kinase 1 (PDK1), also known as PKB kinase, was identified as the activator of the survival kinase Akt/PKB. (ecmbio.com)
  • PDK1 is a member of the AGC superfamily of serine/threonine kinases. (ecmbio.com)
  • Clone M146 was generated from a recombinant protein containing amino acid residues in the C-terminal region of human PDK1. (ecmbio.com)
  • The purified antibody detects a 65 kDa* protein corresponding to the apparent molecular mass of PDK1 on SDS-PAGE immunoblots of human A431 cells and mouse brain. (ecmbio.com)
  • PDPK1 is constitutively active and at present, there is no known inhibitor proteins for PDPK1. (wikipedia.org)
  • The central role PI3-K plays in cell survival suggests that a PI3-K inhibitor offers a strategy to increase the antitumor activity of EGFR inhibitors in resistant NSCL tumors that do not express ErbB-3. (aacrjournals.org)
  • The decreased glucose tolerance caused by PX-866 was insensitive to the AMP-activated protein kinase inhibitor metformin but reversed by insulin and by the peroxisome proliferator-activated receptor-γ activator pioglitazone. (aacrjournals.org)
  • The phosphoinositide 3-kinase inhibitor alpelisib restores actin organization and improves proximal tubule dysfunction in vitro and in a mouse model of Lowe syndrome and Dent disease. (omicsdi.org)
  • kinase inhibitor 2X-amino-3X-methoxyflavone ŽPD98059. (dadospdf.com)
  • but not by the phosphoinositide 3-kinase inhibitor wortmannin. (dadospdf.com)
  • 2012) a novel pkb/akt inhibitor, mk-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle. (roblesdance.shop)
  • In 2013, the Raf family kinase inhibitor Sorafenib (BAY 43-9006) was approved by the FDA for the treatment of advanced renal carcinoma. (biovision.com)
  • Phosphorylated Grb14 is an endogenous inhibitor of retinal protein tyrosine phosphatase 1B, and light-dependent activation of Src phosphorylates Grb14. (ouhsc.edu)
  • Recommended biologic agents for first-line therapy include Bruton tyrosine kinase (BTK) inhibitors, a B-cell lymphoma inhibitor (venetoclax), and monoclonal antibodies. (medscape.com)
  • Currently recommended non-chemotherapy regimens for CLL include monotherapy and combination therapy with agents such as Bruton tyrosine kinase (BTK) inhibitors, monoclonal antibodies, and a B-cell lymphoma inhibitor, among others. (medscape.com)
  • In order to discover the mechanism of etoposideinduced enhance in mTOR protein level, HCT116 p53+/+ and p53-/- cells have been either treated with cycloheximide, an inhibitor of protein synthesis, or the proteasome inhibitor, MG-132 (Figure 2C). (5htreceptor.com)
  • Moreover, phosphorylates and activates RPS6KB1 and RPS6KB2 that promote protein synthesis by modulating the activity of their downstream targets including ribosomal protein S6, eukaryotic translation initiation factor EIF4B and the inhibitor of translation initiation PDCD4. (ucsc.edu)
  • Furthermore, treatment with the myosin light chain kinase (MLCK) inhibitor ML-7 caused cleavage furrow regression and loss of both F-actin and phosphorylated myosin regulatory light chain from the contractile ring in a manner similar to treatment with U73122 and ET-18-OCH3. (diferencias-entre.org)
  • Instead, the presence of inhibitor of apoptosis proteins may possibly directly reduce the activity of caspase 3 antagonizing the method of apoptosis. (camkkinases.com)
  • SMA-RL71 was extremely steady and experienced a diameter of 181.6 nm in buffer and 275.1 nm in serum as measured by dynamic light scattering and a near neutral charge of ?0.0432 mV.30 We first examined the tissue distribution pattern LGK-974 kinase inhibitor of SMA-RL71 and compared it to free RL71. (insulin-receptor.info)
  • Open up in another screen LGK-974 kinase inhibitor Amount 1 Medication deposition in tissue following treatment with SMA-RL71 and RL71. (insulin-receptor.info)
  • Records: Tumor-bearing mice had been treated with (A) an individual iv dosage of 10 mg/kg of either RL71 or SMA-RL71 and euthanized 6 h afterwards or (B) intravenously implemented 10 mg/kg of RL71 or SMA-RL71 LGK-974 kinase inhibitor on times 4, 7, 11, and 14 and euthanized 3 times afterwards. (insulin-receptor.info)
  • It is a potent inhibitor of human neutrophil adhesion to biological surfaces as well as adhesion-dependent granule exocytosis and oxidative burst. (enzolifesciences.com)
  • Dasatinib (Sprycel) was developed as a tyrosine kinase inhibitor targeting Bcr-Abl and the family of Src kinases. (biomedcentral.com)
  • Since dasatinib is a promiscuous kinase inhibitor, possibly affecting multiple disease-relevant pathways, we also determined if basal phospho-protein amounts and treatment-induced changes in phospho-protein levels are indicative of dasatinib responsiveness. (biomedcentral.com)
  • Dasatinib (N-(2-chloro-6-methyl-phenyl)-2-((6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1,3-thiazole-5-carboxamide) is an orally active tyrosine kinase inhibitor developed to target Bcr-Abl and the family of Src kinases [ 1 ]. (biomedcentral.com)
  • Recent work shows that phosphatidylinositol-3-kinase (PI3-K) is coupled to the EGFR only in NSCLC cell lines expressing ErbB-3 and that EGFR inhibitors do not inhibit PI3-K signaling in these cells. (aacrjournals.org)
  • Using a panel of isoform-selective inhibitors, we show that insulin signalling to Akt/PKB (protein kinase B) is attenuated by the additive effects of inhibiting p110? (omicsdi.org)
  • In vitro we exhibited that IL-5 stimulates the selective chemokinesis of bone tissue marrow eosinophils, an activity markedly inhibited by two structurally specific inhibitors of phosphatidylinositol 3-kinase, wortmannin and "type":"entrez-nucleotide","attrs":"text message":"LY294002″,"term_id":"1257998346″,"term_text message":"LY294002″LY294002. (careersfromscience.org)
  • In addition to a role in controlling tumors with Ras mutations and activated growth factor receptors, Raf kinase inhibitors may harbor therapeutic potential in tumors carrying a BRAF oncogene. (biovision.com)
  • These inhibitors prevent the expression of Raf protein, block Ras/Raf interaction, or obstruct its kinase activity. (biovision.com)
  • Several Raf kinase inhibitors are currently undergoing clinical evaluation. (biovision.com)
  • BioVision is proud to offer Sorafenib as well as several other Raf kinase inhibitors for research. (biovision.com)
  • TS-037671 - Novel non-peptidomimetic molecules for use as anti-cancer inhibitors of signal transducer and activator of transcription 3. (osu.edu)
  • Dasatinib has been and still is being tested as a single agent and in combination therapies, for example together with other kinase inhibitors or genotoxic chemotherapeutics, in haematological cancers and solid tumours. (biomedcentral.com)
  • Strategies to prevent acquired endocrine resistance include inhibition of cell-cycle progression in breast cancer cells using cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • SMAD-dependent and SMAD-independent BMP9 signalling pathways during osteogenesis. (portlandpress.com)
  • Dysregulation of AKT-dependent pathways is associated with the development and maintenance of various solid tumours such as those of the lung, prostate, endometrium, cervix, skin and breast [ 5-7 ]. (portlandpress.com)
  • PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. (bio-rad-antibodies.com)
  • PKN1 is a ubiquitously expressed kinase that, when phosphorylated by TRAF1, plays a critical role in the negative regulation of tonic activity of JNK and NF-kappaB signalling pathways. (innatedb.com)
  • Oxaliplatin (Eloxatin) IC50 The primary pathways inside the insulin signaling network (ISN) are more developed [1,2,3], using the serine/threonine proteins kinase Akt/PKB and both mammalian Focus on Of Rapamycin Complexes (mTORC1 and mTORC2) playing a particular role. (gasyblog.com)
  • IL-2-JAK1/3 signaling pathways thus increased the abundance of nutrient transporters, nutrient sensors, and critical oxygen-sensing molecules. (babraham.ac.uk)
  • Group I mGluRs may also modulate extra signaling pathways and activate an array of downstream effectors, including phospholipase D and many proteins kinase pathways, such as for example casein kinase 1, Jun kinase, cyclin-dependent proteins kinase 5, the mammalian focus on of rapamycin (mTOR)/p70 S6 kinase pathway and the different parts of the mitogen-activated proteins kinase/extracellular receptor kinase (MAPK/ERK) pathway [10,11,12]. (annumed.net)
  • Group II and III mGluRs activate various other signaling pathways also, including MAPK and phosphatidylinositol 3-kinase (PI3 kinase) pathways [13]. (annumed.net)
  • Differential gene expression between Duroc and PiNN muscle samples were associated with protein ubiquitination, stem cell pluripotency, amyloid processing, and 3-phosphoinositide biosynthesis and degradation pathways. (ijbs.com)
  • Other pathways in the protein-kinase-activity enriched module were positively correlated with STO (r=0.93), while negatively correlated with FTO (r = -0.72). (ijbs.com)
  • Our results highlight the importance of mitochondria for the oxidative capacity of porcine muscle and for breed-dependent molecular pathways in muscle cell fibers. (ijbs.com)
  • Translocation of the hexokinase rate-limiting enzyme from the cytosol into the outer mitochondrial membrane, where it interacts with voltage-dependent anion channels, can disrupt caspase-dependent cytochrome release, which suppresses the apoptotic pathways of cancer cells and makes cancer more resistant to chemotherapy. (ketotrakmeter.com)
  • The stretch-induced TLR4 is mediated through activation of p38 MAP kinase and NF-κB pathways. (biomedcentral.com)
  • In summary, PRIP-1 is a multifaceted P4-inducible scaffold protein that gates the activity of major signal transduction pathways in the endometrium. (elsevier.com)
  • This example illustrates the fact that the chemical synthesis of proteins or protein domains makes it possible to incorporate any kind of natural or unnatural amino acid at the position of choice, thereby enabling the facile preparation of specific biosensors, enhanced detection systems for drug screening, or the synthesis of activated proteins, e.g. phosphorylated proteins involved in signaling pathways, as defined molecular species. (embl.de)
  • The atypical protein kinase C (PKC) member PKC-zeta has been implicated in several signal transduction pathways regulating differentiation, proliferation or apoptosis of mammalian cells. (embl-heidelberg.de)
  • Galpha12 and Galpha13 regulate extracellular signal-regulated kinase and c-Jun kinase pathways by different mechanisms in COS-7 cells. (ucdenver.edu)
  • Distinct cell cycle timing requirements for extracellular signal-regulated kinase and phosphoinositide 3-kinase signaling pathways in somatic cell mitosis. (ucdenver.edu)
  • PLC-dependent pathways thus play key functions in promoting.Cell treated similarly is shown in Physique ?Figure5A5A. (diferencias-entre.org)
  • Most notably, we discuss their selective interactions with protein kinase and lipid kinase signalling cascades (i.e. phosphoinositide-3 kinase/Akt and mitogen-activated protein kinase pathways), which regulate transcription factors and gene expression involved in both synaptic plasticity and cerebrovascular blood flow. (cambridge.org)
  • There effects are predominately mediated through, but not limited to cannabinoid receptor-1, cannabinoid receptor-2, and G-protein-coupled receptor 55 pathways. (weedneed.org)
  • STAT proteins also known as Signal Transducer and Activator of Transcription are transcription factors involved in a huge repertoire of biological signal transduction cascades leading to embryonic development, programmed cell death, organogenesis, innate immunity, adaptive immunity and cell growth regulation in organisms ranging from insects to man. (biovision.com)
  • The proteolytic activation of this kinase by caspase-3 or related proteases during apoptosis suggests its role in signal transduction related to apoptosis. (innatedb.com)
  • Phosphoinositide-specific phospholipase C (PI-PLC) plays a pivotal role in regulation of intracellular signal transduction from various receptor molecules. (embl.de)
  • The C2 domain is a Ca 2+ -dependent membrane-targeting module found in many cellular proteins involved in signal transduction or membrane trafficking. (embl-heidelberg.de)
  • By this basic mechanism, protein kinases mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. (insulin-receptor.info)
  • Several downstream substrates of activated AKT play a major role in the regulation of cell size, cell cycle progression, glucose metabolism, genome stability, transcription, protein synthesis and inhibition of pro-apoptotic proteins [ 1-4 ]. (portlandpress.com)
  • Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream mediators have yet been identified. (novartis.com)
  • Reduced kinase activities of the insulin receptor (INSR) and several downstream INSR signaling intermediates (i.e. p70S6k, AMP-activated protein kinase, glycogen synthase kinase-3, and Fyn) were detected in adipocytes and T lymphocytes due to short-term treatment with dexamethasone (DEX), a synthetic fluorinated GC. (rug.nl)
  • The simple phosphoinositide PtdIns3 P has been shown to control cell growth downstream of amino acid signalling and autophagy downstream of amino acid withdrawal. (silverchair.com)
  • Group II and III mGluRs are combined to Gi/o protein mostly, which inhibit adenylyl cyclase and straight regulate ion stations as well as other downstream signaling substances via discharge of G subunits. (annumed.net)
  • It prevents apoptosis of proliferating stromal cells and contributes to the relative autonomy of decidual cells by silencing PLC signaling downstream of G q protein-coupled receptors. (elsevier.com)
  • The activated IR kinase phosphorylates substrate proteins on Tyr residues, and these phosphorylated Tyr residues serve as docking sites for downstream effectors ( Fig. 1 ). (diabetesjournals.org)
  • This modified signaling downstream of EGFR1 to increase its autophosphorylation and activation of the proinvasive kinase PKB/Akt. (rupress.org)
  • This action results in reactivation of AMP-ACTIVATED PROTEIN KINASE activity and downstream signaling aimed at decreased metabolism. (nih.gov)
  • We also attempted to elucidate the underlying mechanisms by investigating the involvement of AMP-activated protein kinase, p38 MAPK and eNOS. (biomedcentral.com)
  • Overall, we postulate here a molecular mechanism for GC-induced insulin resistance based on nongenomic GR-dependent inhibition of insulin signaling. (rug.nl)
  • We previously reported that the inhibition of Akt by inositol 1,3,4,5,6-pentakisphosphate (InsP(5)) results in anti-tumour properties. (bath.ac.uk)
  • Here, we investigated the effects of glycogen synthase kinase 3 (GSK3) inhibition via lithium chloride (LiCl) treatment on SERCA uncoupling in skeletal muscle and UCP1 expression in adipose. (jbc.org)
  • Targeting eIF4F translation complex sensitizes B-ALL cells to tyrosine kinase inhibition. (uci.edu)
  • Incubation of cells with cycloheximide alone resulted in inhibition of mTOR protein suggesting a requirement for ongoing protein synthesis to sustain basal mTOR levels. (5htreceptor.com)
  • Inhibition of mitogen-activated kinase signaling sensitizes HeLa cells to Fas receptor-mediated apoptosis. (ucdenver.edu)
  • Alter, J., Rozentzweig, D., and Bengal, E. (2008) Inhibition of myoblast differentiation by tumor necrosis factor alpha is mediated by c-Jun N-terminal kinase 1 and leukemia inhibitory factor . (technion.ac.il)
  • Open up in another window Amount 7 Inhibition of HO-2 activity by QC-308.Enzyme activity was dependant on measuring the CO stated in 15 min from 50 M methemalbumin using 0.5 mg/mL rat brain microsomes. (capecodmushroom.org)
  • Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB (By similarity). (cansar.ai)
  • Feedback regulation of Raf-1 and mitogen-activated protein kinase (MAP) kinase kinases 1 and 2 by MAP kinase phosphatase-1 (MKP-1). (ucdenver.edu)
  • The p85α subunit of phosphatidyl inositol 3 kinase (PIK3R1) and the regulatory subunit 3 of protein phosphatase 1 (PPP1R3) were selected as candidate genes because both encode key proteins involved in insulin signalling and because polymorphisms in these genes have been previously implicated in insulin resistance or type II diabetes. (bmj.com)
  • Here, we targeted phosphatidyl inositol 3 kinase (PI3-K) and protein phosphatase 1 (PP1) because they are key components of the insulin signalling pathway. (bmj.com)
  • Lysates from Jurkat cell line were probed with purified mouse anti-PKCα (pT497) monoclonal antibody at concentrations of 4.0 (lanes 1 and 4), 2.0 (lanes 2 and 5), and 1.0 µg/ml (lanes 3 and 6) with (lanes 1-3) or without (lanes 4-6) lambda protein phosphatase treatment. (bdbiosciences.com)
  • The IL-2 receptor couples to JAK tyrosine kinases and activates the STAT5 transcription factors. (babraham.ac.uk)
  • DAG activates proteins kinase C (PKC) and IP3 BAY-876 induces intracellular calcium mineral discharge from intracellular shops and activates PKC. (annumed.net)
  • Strong calcium entry activates mitochondrial superoxide generation, upregulating kinase signaling in hippocampal neurons. (jefferson.edu)
  • Phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac Exchanger 2 (P-Rex2) is a guanine nucleotide exchange factor (GEF) that specifically activates Rac GTPases, important regulators of actin cytoskeleton remodeling. (biomedcentral.com)
  • Mos stimulates MAP kinase in Xenopus oocytes and activates a MAP kinase kinase in vitro. (ucdenver.edu)
  • These final results are constant using a previous reportFigure 2: (A) Etoposide induced raise in mTOR is ATM-dependent and p53-independent. (5htreceptor.com)
  • B) Etoposide induced improve in mTOR is ATR-dependent. (5htreceptor.com)
  • Nevertheless, the etoposide-mediated improve in mTOR protein accumulation was nonetheless observed in both p53+/+ and p53-/- HCT116 cells within the presence of cycloheximide, indicating that etoposide-mediated raise in mTOR was unlikely due to increased protein synthesis. (5htreceptor.com)
  • Homo sapiens mechanistic target of rapamycin kinase (MTOR), mRNA. (ucsc.edu)
  • The kinase activity of MTOR within the mTORC1 complex is positively regulated by MLST8 and negatively regulated by DEPTOR and AKT1S1. (ucsc.edu)
  • Boosts the protein synthesis enzyme (mTOR) by 800%, prompting the body to build muscle tissue. (t-nation.com)
  • Phosphatidic acid is a naturally occurring mTOR activator that rapidly increases muscle protein synthesis, prompting the body to build muscle. (t-nation.com)
  • The PH domain functions mainly in the interaction of PDPK1 with phosphatidylinositol (3,4)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate which is important in localization and activation of some of membrane associated PDPK1's substrates including AKT. (wikipedia.org)
  • The activation of PDPK1's main effector, AKT, is believed to require a proper orientation of the kinase and PH domains of PDPK1 and AKT at the membrane. (wikipedia.org)
  • Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction: ATP protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate. (systemsbiology.net)
  • In a humanized OcrlY/- mouse model, alpelisib reduced endosomal actin staining while restoring stress fiber architecture and levels of megalin at the plasma membrane of proximal tubule cells, reflected by improved endocytic uptake of low molecular weight proteins in vivo. (omicsdi.org)
  • MCC/eisosomes are membrane microdomains that have been proposed to participate in the plasma membrane function in particular by regulating the homeostasis of lipids, promoting the recruitment of specific proteins and acting as provider of membrane reservoirs. (biomedcentral.com)
  • Activation and membrane binding of retinal protein kinase Balpha/Akt1 is regulated through light-dependent generation of phosphoinositides. (ouhsc.edu)
  • Phosphatidylinositol transfer proteins (PITPs) mediate the transfer of phosphatidylinositol (PtdIns) or phosphatidylcholine (PtdCho) between two membrane compartments, thereby regulating the interface between signalling, phosphoinositide (PI) metabolism and membrane traffic. (silverchair.com)
  • A study by White et al (2009) found that psychosine's cytotoxic effects on oligodendroglia and Schwann cells was mediated through disruption of the architecture and composition of lipid rafts (cell membrane regions characterized by high cholesterol and sphingolipid concentration), followed by altered protein kinase C (PKC) function. (medscape.com)
  • These results indicate that Ras directly regulates phosphoinositide breakdown through membrane targeting of PLCepsilon. (embl.de)
  • The C2 domain is thought to be involved in calcium-dependent phospholipid binding [ ( PUBMED:8253763 ) ] and in membrane targetting processes such as subcellular localisation. (embl-heidelberg.de)
  • We report here the identification of a cytoplasmic and membrane-associated protein that we name zeta-interacting protein (ZIP) and that interacts with the regulatory domain of PKC-zeta but not classic PKCs. (embl-heidelberg.de)
  • This was indicated by less plasma membrane alteration, an amelioration of the loss of mitochondria membrane potential, a decrease in caspase-8 and caspase-3 activation, a decrease in DNA fragmentation factor-45/35 cleavage, and a reduction in the breakage of DNA when compared with Jurkat cells cultured alone. (aai.org)
  • Here we show that blocking the adhesive function of αvβ3 integrin with soluble RGD ligands, such as osteopontin or cilengitide, promoted association of Rab-coupling protein (RCP) with α5β1 integrin and drove RCP-dependent recycling of α5β1 to the plasma membrane and its mobilization to dynamic ruffling protrusions at the cell front. (rupress.org)
  • The increased I glu was paralleled by increased EAAT3 protein abundance in the oocyte cell membrane. (elsevier.com)
  • Many growth factors, cytokines, hormones like insulin and their receptors relay intracellular signals through STAT proteins. (biovision.com)
  • Tyrosine kinases (for example: Janus Kinase/JAK) associated to the growth factor/cytokine receptors phosphorylate STAT proteins which results in their dimerization and transport into the nucleus followed by binding to target gene regulatory elements thus controlling gene expression. (biovision.com)
  • These receptors are characterized by a large extracellular N-terminal domain, known as the Venus flytrap site (VFD), which provides the orthosteric ligand binding site [3]. (annumed.net)
  • G protein-coupled receptors (GPCRs), including chemokine receptors on leukocytes, signal through G protein Gβγ subunits. (acrabstracts.org)
  • Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. (archives-ouvertes.fr)
  • The roles of bile acids and their receptors, such as the nuclear receptor farnesoid X receptor (FXR) and the G protein-coupled receptor TGR5, on the development of NASH are not fully clear. (jbc.org)
  • PubChem]Opiate receptors are coupled with G-protein receptors and function as both positive and negative regulators of synaptic transmission via G-proteins that activate effector proteins. (t3db.ca)
  • Accumulating evidence has demonstrated that steroids can also trigger biological effects by directly binding G-protein-coupled receptors (GPCRs), yet physiological roles of such unconventional steroid signaling in controlling alcohol-induced behaviors remain unclear. (sdbonline.org)
  • These findings provide the first evidence for the involvement of nongenomic G-protein-coupled steroid receptors in the response to alcohol, and shed new light on the potential roles of steroids in alcohol-use disorders. (sdbonline.org)
  • G-protein-coupled receptors (GPCRs) for steroid hormones mediate unconventional steroid signaling. (sdbonline.org)
  • G protein-coupled receptors in cell signaling. (pharmaceuticalintelligence.com)
  • nevertheless, there is evidence of altered insulin signalling as the abundance of insulin receptors is increased and tyrosine kinase activity 4 is decreased in the brain of AD patients compared with control subjects. (bmj.com)
  • The types of receptors to which they bind are varied in structure and possess a variety of enzymatic activities, however, they are all protein in nature. (biologyreference.com)
  • However, uropod-localized receptors and ezrin/radixin/moesin proteins still cluster in nocodazole-treated cells, indicating that MTs are required specifically for uropod stability. (exeter.ac.uk)
  • Hawkins, P. T., Jackson, T. R. & Stephens, L. R. Platelet-derived growth factor stimulates synthesis of PtdIns(3,4,5)P3 by activating a PtdIns(4,5)P2 3-OH kinase. (nature.com)
  • These opposing effects depend in part on the existence of distinct complexes of Vps34 (vacuolar protein sorting 34), the kinase responsible for the majority of PtdIns3 P synthesis in cells: one complex is activated after amino acid withdrawal to induce autophagy and another regulates mTORC1 (mammalian target of rapamycin complex 1) activation when amino acids are present. (silverchair.com)
  • The mTORC1 substrate p70S6 kinase 1 (S6K1) is certainly mixed up in regulation of proteins synthesis as well as the development of cell size, and energetic S6K1 inhibits IRS1 in a poor reviews loop [3]. (gasyblog.com)
  • Interleukin-2 (IL-2) and Janus kinases (JAKs) regulate transcriptional programs and protein synthesis to promote the differentiation of effector CD8 cytotoxic T lymphocytes (CTLs). (babraham.ac.uk)
  • impactjournals.com/oncotarget 429 Oncotargetdemonstrating a requirement of ATM for the initial transient boost in protein synthesis induced by DNA damage that was mediated by mTORC1 [26]. (5htreceptor.com)
  • Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. (ucsc.edu)
  • In parallel to protein synthesis, also regulates lipid synthesis through SREBF1/SREBP1 and LPIN1. (ucsc.edu)
  • Sudden exposure to elevated temperatures results in the synthesis of a set of proteins that protect the cell from heat damage. (biologyreference.com)
  • Liver qi is involved in the processing of macronutrients into molecules to fuel energy metabolism in brain neurons, as well as the synthesis of plasma proteins that maintain blood circulation to the brain, thereby enabling these fuel molecules to be delivered to the brain. (scirp.org)
  • This paper shows Par6G as a negative regulator of the phosphatidylinositol 3'-kinase/phosphoinositide-dependent protein kinase 1/Akt pathway and epithelial cell proliferation and evidence for frequent inactivation of Par6G gene in epithelial cancers. (nih.gov)
  • DJ-1 is a multifunctional protein involved in Parkinson disease (PD) that can act as antioxidant, molecular chaperone, protease, glyoxalase, and transcriptional regulator. (extremalby.com)
  • Therefore, kinetochore proteins may be novel regulator in tumor development and progression, the further elucidating molecular biological mechanism of which may contribute to the accurate targeted therapy of tumors. (researchsquare.com)
  • Serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. (ucsc.edu)
  • It functions as a negative regulator of CELL PROLIFERATION and NEOPLASTIC CELL TRANSFORMATION and is commonly fused with cellular abl protein to form BCR-ABL FUSION PROTEINS in PHILADELPHIA CHROMOSOME positive LEUKEMIA patients. (nih.gov)
  • Recently, linc00152 (an lncRNA) was identified as a potent oncogene in various cancer types, and shown to be involved in cancer cell proliferation, invasiveness, and motility by sponging tumor-suppressive microRNAs acting as a competing endogenous RNA, binding to gene promoters acting as a transcriptional regulator, and binding to functional proteins. (genominfo.org)
  • Nomenclature: akt serine/threonine kinase 1genes: akt1 (hs), akt1 (mm), akt1 (rn). (roblesdance.shop)
  • In the field of biochemistry, PDPK1 refers to the protein 3-phosphoinositide-dependent protein kinase-1, an enzyme which is encoded by the PDPK1 gene in humans. (wikipedia.org)
  • Methods: We treated non-small cell lung carcinoma cells (NSCLCs) with sub-therapeutic, therapeutic, and toxic concentrations of digitoxin and D6MA respectively, followed by both single point and real-time assays to evaluate changes in cellular gene and protein expression, adhesion, elasticity, and migration. (cdc.gov)
  • Global gene expression analysis identified dose-dependent changes to nuclear factor kappa-light-chain-enhancer, epithelial tumor, and microtubule dynamics signaling. (cdc.gov)
  • Phosphoinositide 3-kinase delta gene mutation predisposes to respiratory infection and airway damage. (nature.com)
  • Dominant-activating germline mutations in the gene encoding the PI(3)K catalytic subunit p110delta result in T cell senescence and human immunodeficiency. (nature.com)
  • Potentiation of B2 receptor signaling by AltB2R, a newly identified alternative protein encoded in the human bradykinin B2 receptor gene. (usherbrooke.ca)
  • Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A-related kinase 3. (umbc.edu)
  • Serine/Threonine Kinases (STKs), Never In Mitosis gene A (NIMA)-related kinase 3 (Nek3) subfamily, catalytic (c) domain. (umbc.edu)
  • To do this, the research team carried out a comparative study of neurons in the brains of mice that have this active gene, and others that lack it, with the aim of "comparing the differences between the two protein patterns and, thus, studying the mechanisms that may be altered," explains Raquel Requejo, principal investigator of the study and a member of the BIO126 group at the University of Cordoba. (extremalby.com)
  • The protein encoded by this gene belongs to the protein kinase C superfamily. (innatedb.com)
  • This gene and/or its encoded proteins are associated with 65 experimentally validated interaction(s) in this database. (innatedb.com)
  • Here, gene expression was investigated in malignant hyperthermia syndrome (MHS)-negative Duroc and Pietrian (PiNN) pigs significantly differing for the muscle fiber types slow-twitch-oxidative fiber (STO) and fast-twitch-oxidative fiber (FTO) as well as mitochondrial activity (succinate-dependent state 3 respiration rate). (ijbs.com)
  • miRNAs are encoded in the genome either as independent gene segments or within the introns of protein-coding genes. (cdrjournal.com)
  • NSCLC, which includes lung adenocarcinoma (ADC) and lung squamous cell carcinoma (SCC), represents approximately 85% of all cases [ 2 ] and can be further divided into subgroups according to specific gene mutations [ 3 ]. (aging-us.com)
  • The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. (ucsc.edu)
  • Abbreviations BMBone marrowCAFCancer-associated fibroblastDCDendritic cellDGCR8DiGeorge symptoms critical area gene 8ECEndothelial cellsEMTEpithelial-mesenchymal transitionEVExtracellular vesicleHCCHepatocellular carcinomaIFNInterferon-Mef2cMyocyte enhancer element 2cmiRNAMicroRNAMSCMesenchymal stem cell.MVPMajor vault proteinNF-BNuclear factor kappa BPDPK1Phosphoinositide-dependent protein kinase-1pre-miRNAprecursor miRNApri-miRNAprimary miRNAPTENPhosphatase and tensin homologRISCRNA-induced silencing complexSOCS5Suppressor of cytokine signaling 5TAMTumor-associated macrophageTLRToll-like receptorTregRegulatory T cellZO-1Zonula occludens protein 1 Authors contributions AK, NK, also to drafted the manuscript. (aqualogy.org)
  • Tamir, Y., and Bengal, E. (1998) p53 protein is activated during muscle differentiation and participates with MyoD in the transcription of muscle creatine kinase gene . (technion.ac.il)
  • The zebrafish embryo is an ideal model system for studying PGC migration due to 1) the transparency of the embryo, allowing in vivo analyses of cell migration and development, 2) the availability of various mutant stocks and the morpholino antisense oligo nucleotide gene knockdown system, and 3) the availability of PGC marker genes, for which localisation and functions are well characterised. (exeter.ac.uk)
  • Such lncRNAs participate in gene regulation at the transcriptional and translational levels and in protein activation at the post-translational levels. (genominfo.org)
  • The effect of T-588 on Ca2q reperfusion injury including apoptosis was inhibited by the mitogen-activated protein ŽMAP.rextracellular signal-regulated kinase ŽERK. (dadospdf.com)
  • Bcl-2 proteins forms heterodimer processes with Bax meats, leading to the discharge of cytochrome from the mitochondria and the induction of apoptosis (16). (careersfromscience.org)
  • Liu (17) present that puerarin suppresses the apoptosis of individual osteoblasts TAK-901 by raising the proteins amounts of Bcl-2, while decreasing the known amounts of Bax in a dose-dependent way. (careersfromscience.org)
  • Wang (18) reported that puerarin stops MPP-induced apoptosis of Computer12 cells by suppressing the discharge of mitochondrial cytochrome and account activation of caspase-3. (careersfromscience.org)
  • Many signaling paths, including the phosphoinositide 3-kinase (PI3T)/Akt path and c-Jun N-terminal kinase (JNK) path, have got also been confirmed to regulate the apoptosis of osteoblastic cells (18C22). (careersfromscience.org)
  • The present research focused to check out the results of puerarin on dexamethasone (DEX)-activated apoptosis in hFBO1.19 cells and examine the reflection of several apoptosis-associated meats, including Bcl-2, Bax, cytochrome and caspase-3 were examined, to determine whether the results were mediated by the PI3T/Akt and JNK signaling paths. (careersfromscience.org)
  • Furthermore, the Akt substrate Forkhead container proteins O1 (FoxO1) is certainly mixed up in legislation of proliferation and apoptosis, therefore the insulin signaling network includes a main role not merely in weight problems and diabetes but also in cancers [3,13,14]. (gasyblog.com)
  • PKC is certainly a family group of serine/threonine phospholipid-dependent kinases that are mediators of cell proliferation, differentiation, apoptosis, motility, and adhesion (26, 27). (globaltechbiz.com)
  • Here we studied the protective effect of metformin against free fatty acid-induced apoptosis of human coronary artery endothelial cells (HCAECs) by assessing DNA fragmentation and cleaved caspase 3 levels. (biomedcentral.com)
  • It is thought that several cellular and molecular events are involved, including increases in oxidative stress, impaired mitochondria function, activation of neuronal apoptosis, the deposition of aggregated proteins and excitotoxicity. (cambridge.org)
  • PDPK1 is a master kinase, which is crucial for the activation of AKT/PKB and many other AGC kinases including PKC, S6K, SGK. (wikipedia.org)
  • The STAT proteins can be dephosphorylated by nuclear phosphatases, which lead to their inactivation and they are transported out of the nucleus into the cytosol awaiting the next round of activation signal. (biovision.com)
  • Mediated activation of akt induced expression of the antiapoptotic protein mcl-1. (roblesdance.shop)
  • The kinase cascade through the insulin receptor (IR) up to mTORC1, aswell as the mTORC1 activation by proteins and energy, are obviously assessed [7]. (gasyblog.com)
  • Growth factor receptor-bound protein 14 undergoes light-dependent intracellular translocation in rod photoreceptors: functional role in retinal insulin receptor activation. (ouhsc.edu)
  • Serine/threonine kinase akt activation regulates the activity of retinal serine/threonine phosphatases, PHLPP and PHLPPL. (ouhsc.edu)
  • O-Uchi J, Komukai K, Kusakari Y, Obata T, Hongo K, Sasaki H, Kurihara S. alpha1-adrenoceptor stimulation potentiates L-type Ca2+ current through Ca2+/calmodulin-dependent PK II (CaMKII) activation in rat ventricular myocytes. (jefferson.edu)
  • TS-037569 - The constant activation of Signal Transducer and Activator of Transcription 3 (STAT3) is frequently detected in many cancer patients with advanced diseases. (osu.edu)
  • Metformin, which is used as first line treatment of T2D patients, is believed to exert its pharmacological effects through activation of AMP-activated protein kinase, which has emerged as a new potential target in reversing endothelial dysfunction. (biomedcentral.com)
  • Metformin is believed to exert its pharmacological effects through activation of AMP-activated protein kinase (AMPK) [ 5 ]. (biomedcentral.com)
  • 3 Results and Discussion In order to study GH modulatory effects on hepatic Akt-mediated EGF signaling protein content and activation of Akt were analyzed in solubilized liver from transgenic mice that overexpress GH and in their normal siblings. (rmrfotoarts.com)
  • Rho-family GTPases cycle between an inactive GDP-bound state and an active GTP-bound state, which is regulated by their interactions with a variety of guanine nucleotide exchange factors (GEFs) that promote activation by catalyzing the exchange of GDP for GTP, and GTPase activating proteins (GAPs) that promote inactivation by stimulating the GTPase to hydrolyze GTP to GDP. (biomedcentral.com)
  • Autophosphorylation results in activation of the Tyr kinase activity of the receptor ( 8 ). (diabetesjournals.org)
  • In the inactive state, the catalytic site of the Tyr kinase is occluded by the "activation-loop," preventing access of ATP and various substrates. (diabetesjournals.org)
  • On the other hand, low cellular energy levels can inhibit mTORC1 through activation of PRKAA1 while hypoxia inhibits mTORC1 through a REDD1-dependent mechanism which may also require PRKAA1. (ucsc.edu)
  • Megakaryocytic differentiation induced by constitutive activation of mitogen-activated protein kinase kinase. (ucdenver.edu)
  • Deuterium exchange mass spectrometry as a probe of protein kinase activation. (ucdenver.edu)
  • Constitutive activation of extracellular signal-regulated kinase 2 by synergistic point mutations. (ucdenver.edu)
  • In vitro activation of a myelin basic protein/microtubule-associated protein 2 kinase. (ucdenver.edu)
  • Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo autophosphorylation on both tyrosine and threonine residues: implications for their mechanism of activation. (ucdenver.edu)
  • Mitogen-activated protein kinase activation is not necessary for, but antagonizes, 3T3-L1 adipocytic differentiation. (ucdenver.edu)
  • Cross-cascade activation of ERKs and ternary complex factors by Rho family proteins. (ucdenver.edu)
  • Activation of serine peptide kinase activity by myelin basic protein kinases in vitro. (ucdenver.edu)
  • Hydrogen-exchange mass spectrometry reveals activation-induced changes in the conformational mobility of p38alpha MAP kinase. (ucdenver.edu)
  • Nevertheless, only a weak expression of active caspase 3 was observed till middle of pregnancy suggesting that if programmed cell death occurs, it ought to be via a mechanism independent of the activation of this executioner caspase. (camkkinases.com)
  • ERM-Dependent Assembly of T Cell Receptor Signaling and Co-stimulatory Molecules on Microvilli prior to Activation. (pasteur.fr)
  • 13] Slessareva, J.E., Routt, S.M., Temple, B., Bankaitis, V.A. and Dohlman, H.G. (2006) Activation of the Phosphatidylinositol 3-Kinase Vps34 by a G Protein Alpha Subunit at the Endosome. (scirp.org)
  • All have C-terminal kinase domains, which are closely related to those of protein kinases A and B (Akt), and variable N-terminal regulatory domains that give them different modes of activation. (bdbiosciences.com)
  • Specifically, the threonine 497 (T497) of PKC α is in the activation loop of the kinase domain and is phosphorylated by the constitutively active phosphoinositide-dependent kinase-1 (PDK-1). (bdbiosciences.com)
  • Development of an O -GlcNAc specific antibody in 2001 by Hart and colleagues [ 3 ] has added some momentum in this field and contributed significantly in the identification of O -GlcNAc modified proteins. (biomedcentral.com)
  • the kinase or catalytic domain and the PH domain. (wikipedia.org)
  • Catalytic domain of the Protein Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1. (umbc.edu)
  • This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. (bio-rad-antibodies.com)
  • Knockdown experiments in undifferentiated HESCs revealed that PRIP-1 maintains basal phosphoinositide 3-kinase/Protein kinase B activity, which in turn prevents illicit nuclear translocation of the transcription factor forkhead box protein O1 and induction of the apoptotic activator BIM. (elsevier.com)
  • Purification and characterization of mitogen-activated protein kinase activator(s) from epidermal growth factor-stimulated A431 cells. (ucdenver.edu)
  • The Hippo signalling pathway restricts cell proliferation in animal tissues by inhibiting Yes-associated protein (YAP or YAP1) and Transcriptional Activator with a PDZ domain (TAZ or WW-domain-containing transcriptional activator [WWTR1]), coactivators of the Scalloped (Sd or TEAD) DNA-binding transcription factor. (figshare.com)
  • We have determined that sfRon plays a significant role in the aggressiveness of breast cancer in vivo by dramatically promoting tumor growth and metastasis [ 3 ]. (genesandcancer.com)
  • Akt (protein kinase b, pkb) is a serine/threonine kinase that plays a key in regulating cell survival, angiogenesis and tumor formation. (roblesdance.shop)
  • MAP kinase pathway consists of kinases such as Raf, MEK1/2, and ERK1/2, etc., that are critical for the proliferation and survival of tumor cells. (biovision.com)
  • Ketogenic diets selectively starve tumors by providing the fat and protein that otherwise could not be used by glucose-dependent tumor cells. (ketotrakmeter.com)
  • Ketogenic diets also amplify adenosine monophosphate-activated protein kinase (AMPK), which inhibits aerobic glycolysis and suppresses tumor proliferation, invasion, and migration. (ketotrakmeter.com)
  • TS-037647 - A novel set of molecules that inhibit integrin-linked kinase in order to suppress tumor cell growth and metastasis. (osu.edu)
  • Mutations in UNC5D promoted tumorigenesis by abolishing the tumor suppressor function of the encoded protein. (aging-us.com)
  • The prevention of cancer is profoundly dependent on the p53 tumor suppressor protein. (biologists.com)
  • Previous studies have reported that various proteins participating in the regulation of mitosis are abundant expressed in human tumor tissues, an amount of which are proved to be carcinogenic[8]. (researchsquare.com)
  • Studies have indicated that kinetocyte proteins are vital in tumor. (researchsquare.com)
  • Once we stated in the Intro, understanding the technique of dormant condition cell survival is essential for avoidance of tumor recurrence, since some metastasized tumor cells are stay and arrested dormant for quite some time [3, 6C8]. (aqualogy.org)
  • These RCP-driven changes in α5β1 trafficking led to acquisition of rapid/random movement on two-dimensional substrates and to a marked increase in fibronectin-dependent migration of tumor cells into three-dimensional matrices. (rupress.org)
  • Thus, sfRon organizes into a constitutively-active receptor with ligand-independent activity [ 3 ]. (genesandcancer.com)
  • Analysis of wild-type and constitutively active mutants of MAP kinase kinase-1. (ucdenver.edu)
  • Transformation of mammalian cells by constitutively active MAP kinase kinase. (ucdenver.edu)
  • Non‑insulin‑dependent diabetes mellitus (NIDDM) is associated with chronic inflammatory activity and disrupted insulin signaling, leading to insulin resistance (IR). (spandidos-publications.com)
  • Non-insulin-dependent diabetes mellitus (NIDDM or type 2 DM), the predominant form of adult-onset DM, is rapidly becoming a global public health emergency ( 1 ). (spandidos-publications.com)
  • In NIDDM, the chronic elevation of inflammatory cytokines and free fatty acids (FFAs) disrupts insulin signaling and, ultimately, causes the degeneration of pancreatic cells ( 3 - 6 ). (spandidos-publications.com)
  • Amino acids require glucose to enhance, through phosphoinositide-dependent protein kinase 1, the insulin-activated protein kinase B cascade in insulin-resistant rat adipocytes. (c3m-nice.fr)
  • Insulin signaling is relevant to memory and cognition modulation, Aβ precursor protein production and clearance, and cerebral glucose metabolism ( Wu and Swaab, 2005 ). (e-jer.org)
  • Both genetic and environmental factors contribute to its pathogenesis, which involves insufficient insulin secretion, reduced responsiveness to endogenous or exogenous insulin , increased glucose production, and/or abnormalities in fat and protein metabolism. (mhmedical.com)
  • Here, we generate a comprehensive description of non-genomic GC effects on insulin signaling using peptide arrays containing 1176 different kinase consensus substrates. (rug.nl)
  • DEX inhibited insulin signaling through a GR-dependent (RU486 sensitive) and transcription-independent ( actinomycin D insensitive) mechanism. (rug.nl)
  • There was excellent correlation between predicted in silico and measured in vitro K D s for binding to the PH domain of AKT, which were in the range 0.4 to 3.6 μmol/L. Some of the compounds exhibited PH domain-binding selectivity for AKT compared with insulin receptor substrate-1 and 3-phosphoinositide-dependent protein kinase 1. (uthscsa.edu)
  • Nevertheless, this watch was questioned in a report that reported experimental period courses of many proteins from the ISN under proteins and insulin excitement [10]. (gasyblog.com)
  • A still different watch emerged from tests in nondiabetic mice both in vivo and in muscle tissue biopsies, and in L6 cells PIK3R5 subjected to a moderate enriched with protein secreted by the tiny intestine of diabetic rats also to serum from insulin resistant human beings [11]. (gasyblog.com)
  • Involvement of insulin/phosphoinositide 3-kinase/Akt signal pathway in 17 beta-estradiol-mediated neuroprotection. (ouhsc.edu)
  • Interaction of the retinal insulin receptor beta-subunit with the p85 subunit of phosphoinositide 3-kinase. (ouhsc.edu)
  • This is observed in diabetic and obese individuals, and the extent of endothelium-dependent vasodilatation correlates with an individual's insulin sensitivity [ 4 ]. (biomedcentral.com)
  • Post-translational modification of proteins at serine and threonine side chains by β- N -acetylglucosamine ( O -GlcNAc) mediated by the enzyme β- N -acetylglucosamine transferase has been emerging as a fundamental regulatory mechanism encompassing a wide range of proteins involved in cell division, metabolism, transcription and cell signaling. (biomedcentral.com)
  • These domains were first discovered as the loci of phorbol ester and diacylglycerol binding to conventional protein kinase C isozymes, which contain 2 C1 domains (C1A and C1B) in their N-terminal regulatory regions. (embl-heidelberg.de)
  • This observation, together with the remarkable pancreatic phenotypic similarities between RasGrf1 KO and Pttg1 KO mice suggested the possibility of proximal functional regulatory links between RasGrf1 and Pttg1 in pancreatic cell lineages expressing these proteins. (biomedcentral.com)
  • Nevertheless, the recombinant proteins found in that research was a GST-fusion derivative which also included Tivozanib a Cys127Ala mutation which disrupts HRM3, among HO-2's heme regulatory motifs (HRMs). (capecodmushroom.org)
  • To achieve these processes, the PM is highly compartmentalized consisting of distinct subdomains with different protein / lipid environments and specialized functions. (biomedcentral.com)
  • However, lipid-dependent signalling almost always exhibits a spatial dimension, related to the site of formation of the lipid signal. (silverchair.com)
  • While some of these proteins may augment the effector functions of CTLs, others may limit their cytotoxicity. (babraham.ac.uk)
  • We found that IL-2 signaling through JAK1 and JAK3 (JAK1/3) increased the abundance of a key subset of proteins to induce the accumulation of critical cytokines and effector molecules in T cells. (babraham.ac.uk)
  • There was a significant dose dependent reduction in the number of effector T cells (20 mg/kg: p=0.0495, 35 mg/kg: p=0.0001) and central memory T cells (35 mg/kg: p=0.0029) in spleens of lupus prone mice. (acrabstracts.org)
  • CONCLUSIONS: The site-specific incorporation of a fluorescent group at a strategic position in a Ras effector protein allows the detection of activated Ras with high sensitivity. (embl.de)
  • Eosinophils are the principal effector cells for allergic inflammation in a variety of diseases, in which they contribute to tissue damage and remodelling processes via the secretion of cytotoxic granular proteins and cytokines. (keele.ac.uk)
  • Calcium-Calmodulin-Dependent Protein Kinases" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (jefferson.edu)
  • This graph shows the total number of publications written about "Calcium-Calmodulin-Dependent Protein Kinases" by people in this website by year, and whether "Calcium-Calmodulin-Dependent Protein Kinases" was a major or minor topic of these publications. (jefferson.edu)
  • Below are the most recent publications written about "Calcium-Calmodulin-Dependent Protein Kinases" by people in Profiles. (jefferson.edu)
  • Generally, group I mGluRs few to Gq/G11 proteins and activate phospholipase C, which outcomes in the hydrolysis of phosphoinositides and era of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). (annumed.net)
  • Regulation of phospholipase D and secretion in mast cells by protein kinase A and other protein kinases. (jefferson.edu)
  • Here, we show that PLCL1, coding phospholipase C (PLC)-related catalytically inactive protein 1 (PRIP-1), is highly induced in response to P4 signaling in decidualizing human endometrial stromal cells (HESCs). (elsevier.com)
  • In addition, both PIP2 and phosphoinositide-specific phospholipase C (PLC) have been localized to the cleavage furrow of dividing mammalian cells. (diferencias-entre.org)
  • Glucocorticoids (GCs) are powerful immunosuppressive agents that control genomic effects through GC receptor (GR)-dependent transcriptional changes. (rug.nl)
  • Everolimus also dramatically reduced estrogen receptor (ER) expression (mRNA and protein) and transcriptional activity in addition to the ER chaperone, heat shock protein 90 protein (HSP90). (biomedcentral.com)
  • PTEN knockdown induced the up-regulation of ER transcriptional activity in MCF-7 cells but decreased ER protein levels and transcriptional activity in T47D and MDA-361 cells. (aacrjournals.org)
  • Tamir, Y., and Bengal E . (2000) Phosphoinositide 3-kinase induces the transcriptional activity of MEF2 proteins during muscle differentiation . (technion.ac.il)
  • C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. (bio-rad-antibodies.com)
  • These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. (ucsc.edu)
  • Responses to DNA damage and regulation of cell cycle checkpoints by the ATM protein kinase family. (wikidata.org)
  • A serine-threonine kinase which plays an important role in the regulation of electrolyte homeostasis, cell signaling, survival, and proliferation. (ucdenver.edu)
  • Non-canonical regulation of phosphatidylinositol 3-kinase gamma isoform activity in retinal rod photoreceptor cells. (ouhsc.edu)
  • AKT, also known as protein kinase B, is an oncoprotein involved in regulation of cellular proliferation, survival, motility and angiogenesis. (bmj.com)
  • Measurement of Rab5 protein kinase B/akt and regulation of ras-activated endocytosis. (embl.de)
  • Furthermore, he observes - Millions of years later, or as soon as, the information of interaction leading to activity and regulation could be found in RNA, proteins like reverse transcriptase move this information to a more stable form (DNA). (pharmaceuticalintelligence.com)
  • In the present study, we used a combination of techniques to measure ER stability and the related G β 1 γ 2 trafficking following muscle mobilization, and demonstrated a temporally and Fyn-dependent up-regulation of Ca 2+ level in the mobilized muscle. (scirp.org)
  • The decreased HIF-1alpha expression was not dependent on VHL interaction because a renal carcinoma cell line with VHL mutation and constitutive high HIF-1alpha expression also showed down-regulation of HIF-1alpha after treatment with LY294002. (ox.ac.uk)
  • It is a serine- threonine protein kinase which plays many functions. (roblesdance.shop)
  • In vitro and in vivo studies suggest that sfRon expression has more potent biological outcomes than those observed with full-length Ron expression, presumably because of the constitutive kinase activity of the sfRon protein [ 3 ]. (genesandcancer.com)
  • In vivo effect of compounds was tested on PC3 xenografts, whereas in vitro activity on kinases was determined by SelectScreen Kinase Profiling Service. (bath.ac.uk)
  • RESULTS: The derivative 2-O-benzyl-myo-inositol 1,3,4,5,6-pentakisphosphate (2-O-Bn-InsP(5)) is active towards cancer types resistant to InsP(5) in vitro and in vivo. (bath.ac.uk)
  • 1) Es konnten strahlenresistente Tumorzellpopulationen der Linien A549 (NSCLC) und SK-BR-3 (Brustkrebs) mittels eines Radioselektionsprozesses in vitro isoliert werden. (uni-hohenheim.de)
  • Furthermore, using a liposome-based reconstitution assay, it is shown that the phosphatidylinositol 4,5-bisphosphate-hydrolyzing activity of PLCepsilon is stimulated in vitro by Ha-Ras in a GTP-dependent manner. (embl.de)
  • Phosphoproteomics experiments, in vitro kinase assays and pull-down assays were subsequently performed in order to identify the underlying growth inhibitory mechanism. (elifesciences.org)
  • This enzyme is also sometimes dependent on CALCIUM. (jefferson.edu)
  • Here, we report a novel interaction between the mitotic kinase, Aurora A, and the glycolytic enzyme, pyruvate kinase M2 (PKM2), in the interphase of the cell cycle. (jbc.org)
  • A mediator of Rho-dependent invasion moonlights as a methionine salvage enzyme. (ucdenver.edu)
  • Several PDPK1 substrates including S6K and Protein kinase C, require the binding at this docking site. (wikipedia.org)
  • STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. (umbc.edu)
  • To time, research have got indicated that there are two main apoptotic paths: the extrinsic, or loss of life receptor, TAK-901 path and the inbuilt, or mitochondrial, path (14), B-cell-associated A proteins (Bax) and B-cell lymphoma (Bcl)-2 are associates of the Bcl-2 family members, which is certainly carefully linked with the mitochondrial TAK-901 apoptotic path (15). (careersfromscience.org)
  • Sarco(endo)plasmic reticulum Ca 2+ -ATPase (SERCA) uncoupling in skeletal muscle and mitochondrial uncoupling via uncoupling protein 1 (UCP1) in brown/beige adipose tissue are two mechanisms implicated in energy expenditure. (jbc.org)
  • Predicted to enable protein kinase C binding activity. (nih.gov)
  • To conclude, knock-down of Angptl8 in adipocytes suggests that the protein acts to inhibit intracellular lipolysis, analogous to its activity in the circulation. (helsinki.fi)
  • Effects of peroxisome proliferator-activated receptor γ in simvastatin antiplatelet activity: influences on cAMP and mitogen-activated protein kinases. (semanticscholar.org)
  • Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. (umbc.edu)
  • Gel shifting assay showed significant increase of DNA-protein binding activity of NF-κB after stretch and SB203580 abolished the DNA-protein binding activity induced by cyclic stretch. (biomedcentral.com)
  • Breakpoint cluster region-homology (BH) domain in p85α has shown GTPase activating protein (GAP) activity toward Rab family. (biomedcentral.com)
  • Effects of phorbol ester on mitogen-activated protein kinase kinase activity in wild-type and phorbol ester-resistant EL4 thymoma cells. (ucdenver.edu)
  • Interdependent domains controlling the enzymatic activity of mitogen-activated protein kinase kinase 1. (ucdenver.edu)
  • Application of DopEcR's ligands, ecdysone and dopamine, had different effects on nicotine-induced Ca2+-responses in the MB: ecdysone enhanced activity in the calyx and cell body region in a DopEcR-dependent manner, whereas dopamine reduced activity in the medial lobes independently of DopEcR. (sdbonline.org)
  • In parallel, Fyn activity in ER was gradually decreased, which was accompanied by enhanced PTP1B activity and expressions of ER proteins (calnexin, Grp94, cyclophilin, and Hsp70). (scirp.org)
  • It also has activity as a GTPASE-ACTIVATING PROTEIN for RAC1 PROTEIN and CDC42 PROTEIN . (nih.gov)
  • In addition, lncRNAs can interact with proteins possessing RNA binding motifs and increase their stability and activity [ 7 , 8 ]. (genominfo.org)
  • Western blot analysis of whole cell lysates probed with Mouse anti Human PI-3 kinase C2 subunit alpha antibody, clone OTI1B8 ( VMA00263 ) followed by detection with HRP conjugated Goat anti Mouse IgG (1/10,000, STAR207P ) and visualized on the ChemiDoc MP with 68 second exposure. (bio-rad-antibodies.com)
  • Arrow points to PI-3 kinase C2 subunit alpha (molecular weight 191 kDa). (bio-rad-antibodies.com)
  • Given the role of AKT as a critical signalling hub for tumour survival, significant efforts have been made to target this kinase for many years. (portlandpress.com)
  • Overall 5-year survival is approximately 50%, and treatment consists of en bloc surgical resection followed by high-dose conformal radiation therapy (RT) such as proton beam radiation. (medscape.com)
  • PKB/Akt: connecting phosphoinositide 3-kinase to cell survival and beyond. (wikidata.org)
  • Akt is a serine/threonine-specific protein kinase that plays a critical role in controlling the balance between survival and death. (roblesdance.shop)
  • By contrast, loss of this scaffold protein did not compromise survival of decidual cells. (elsevier.com)
  • The intracellular protein B\cell\lymphoma\2 (BCL2) continues to be considered a good target for cancer therapy because the finding of its work as a significant promoter of cell survival (an anti\apoptotic) in the past due 1980s. (capecodmushroom.org)
  • Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. (cusabio.com)
  • T2 - Beyond a master kinase in the cytosol? (uky.edu)
  • It was also found that DopEcR may promote ethanol sedation by suppressing epidermal growth factor receptor /extracellular signal-regulated kinase signaling. (sdbonline.org)
  • Two fluorescent amino acids with structures based on the nitrobenz-2-oxa-1,3-diazole and coumaryl chromophores were incorporated at a site which is close to the RBD/Ras.GTP binding surface. (embl.de)
  • PAR3beta, a novel homologue of the cell polarity protein PAR3, localizes to tight junctions. (nih.gov)
  • Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C. Noda Y, et al . (nih.gov)
  • Mast cell degranulation increases mouse Mast Cell Protease 4-dependent vasopressor responses to big endothelin-1 but not Angiotensin I. (usherbrooke.ca)
  • The high mortality rate is attributed to its early metastasis, especially in cases of non-small cell lung carcinoma (NSCLC) ( 1 - 3 ). (spandidos-publications.com)
  • In vivo studies have demonstrated that cell lines bearing the H1047R point mutation, the most frequent cancer-specific mutation in the kinase domain of p110? (omicsdi.org)
  • The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), which is also involved in actin polymerization and cell migration, is downregulated by the H1047R mutation in p110? (omicsdi.org)
  • can block phosphoinositide 3-kinase signalling and tumour growth in certain cell types. (omicsdi.org)
  • Tozasertib Bone tissue marrow leukocytes (3 106 cells in 0.2 ml assay buffer) had been placed in top of the chamber of Transwell filters (3-m pore size) which were in turn put into individual wells of the 24-very well cell culture dish containing 0.3 ml of assay buffer. (careersfromscience.org)
  • The peroxynitrite anion (ONOO - ) produced during this process can nitrate several biomolecules, such as proteins, lipids, and DNA, to generate 3-nitrotyrosine (3-NT), which further induces cell death. (frontiersin.org)
  • This is what is known in the scientific literature as an "aberrant cell cycle" and its relationship "with this neurodegenerative disease and the absence of the DJ1 protein has been described for the first time in this study," said Requejo. (extremalby.com)
  • Deficiency of Parkinson's Related Protein DJ-1 Alters Cdk5 Signaling and Induces Neuronal Death by Aberrant Cell Cycle Re-entry" by Raquel Requejo et al. (extremalby.com)
  • Here, using a comparative proteomic analysis between wild-type cortical neurons and neurons lacking DJ-1 (data available via ProteomeXchange, identifier PXD029351), we show that this protein is involved in cell cycle checkpoints disruption. (extremalby.com)
  • The evaluation revealed simple Oxaliplatin (Eloxatin) IC50 interactions among the concentrations of ISN protein and the variables from the cell inhabitants model that characterize cell routine development and cell loss of life. (gasyblog.com)
  • The HL60 cell lines were analysed using flow cytometry to find out how PKC (Bisindolylmaleimide I) was expressed in HL60 and whether that expression was dependent on whether PKC is activated or inhibited. (biomedgrid.com)
  • Sorting receptor that directs several proteins to their correct location within the cell (Probable). (cansar.ai)
  • In ERBB2-dependent cancer cells, promotes cell proliferation (PubMed:31138794). (cansar.ai)
  • Mammalian TOR can be a Ser/Thr kinase from the phosphatidylinositol 3-kinase-related kinase proteins family members and a central modulator of cell development. (rmrfotoarts.com)
  • Depression of DNA-PKcs not only sensitizes cells to radiation, but also results in a decrease in cell growth rate and c-Myc protein levels [ 14 ]. (biomedcentral.com)
  • Lymphocytes also respond to other environmental cues, including cytokines and cell surface proteins on neighboring cells. (uci.edu)
  • Cell division is regulated by a variety of proteins at all stages of cell cycle. (researchsquare.com)
  • Kinetochores possesses complex multi-subunit structure that consist of more than 100 different proteins in human cells[9], which is imperative in maintaining the normal division of cell sister chromatid and maintaining chromosomal stability. (researchsquare.com)
  • identified that targeted knockdown of kinetochore protein D40 can prevent neoplasm cell progression[15]. (researchsquare.com)
  • This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. (ucsc.edu)
  • DAG and Ca2+ activate protein kinase C (PKC), which stimulates cell growth [4]. (diferencias-entre.org)
  • Involvement of Ip Address 10 in iPSC CM efficiency Interferon g inducible protein 10, monokine induced by IFN g and the IFN g inducible T cell chemoattractant are three chemokines that bind to a standard receptor, CXCR3. (camkkinases.com)
  • In the tutorial that follows we find support for the view that mechanisms and examples from the current literature, which give insight into the developments in cell metabolism, are achieving a separation from inconsistent views introduced by the classical model of molecular biology and genomics, toward a more functional cellular dynamics that is not dependent on the classic view. (pharmaceuticalintelligence.com)
  • Parallel genome-wide RNAi screens identify lymphocyte-specific protein tyrosine kinase (LCK) as a targetable vulnerability of cell proliferation and chemoresistance in nasopharyngeal carcinoma. (who.int)
  • Identification of G2/M targets for the MAP kinase pathway by functional proteomics. (ucdenver.edu)
  • Targets of SGK1 include the mammalian phosphatidylinositol-3-phosphate-5-kinase PIKfyve (PIP5K3). (elsevier.com)
  • Multiple components in an epidermal growth factor-stimulated protein kinase cascade. (ucdenver.edu)
  • Evidence for an epidermal growth factor-stimulated protein kinase cascade in Swiss 3T3 cells. (ucdenver.edu)
  • Protein kinases are enzymes that transfer a phosphate group from a phosphate donor onto an acceptor amino acid in a substrate protein. (insulin-receptor.info)
  • The IR (IR), which is widely expressed, is a transmembrane tyrosine (Tyr) kinase that is expressed as a tetramer in an α2β2 configuration ( 6 , 7 ). (diabetesjournals.org)
  • quickly, higher mediator or mechanism cytosol can reverse conserved into proteins and electron proteins. (erik-mill.de)
  • The MMP family of human zinc-dependent endopeptidases is responsible for degradation of the ECM components such as collagen, proteoglycan, fibronectin, elastin, and laminin ( 7 ). (spandidos-publications.com)
  • The first family of tetraspanners found in MCCs includes Sur7 and the paralogous proteins Fmp45, Pun1, and Ynl194c. (biomedcentral.com)
  • The receptor tyrosine kinase Ron, which belongs to the MET protooncogene family, has been a focus of cancer research for the last two decades [ 1 ]. (genesandcancer.com)
  • There are seven mammalian STAT family members that have been identified: STAT1, 2, 3, 4, 5 and 6. (biovision.com)
  • The protein kinase family is one of the largest families of proteins in eukaryotes, classified in 8 major groups based on sequence comparison of their tyrosine ,PTK) or serine/threonine ,STK) kinase catalytic domains. (insulin-receptor.info)
  • 11] McGarrigle, D. and Huang, X.Y. (2007) GPCRs Signaling Directly through Src-Family Kinases. (scirp.org)
  • The Protein Kinase C (PKC) family of serine/threonine protein kinases is involved in a number of processes such as growth, differentiation, and cytokine secretion. (bdbiosciences.com)
  • Addition of SB203580, TNF-α antibody, and p38α MAP kinase siRNA 30 min before stretch inhibited the induction of TLR4 protein. (biomedcentral.com)
  • Addition of losartan, TNF-α antibody, or p38α siRNA 30 min before Ang II and TNF-α stimulation significantly blocked the increase of TLR4 protein by AngII and TNF-α. (biomedcentral.com)
  • Mouse monoclonal antibody purified with protein A chromatography is supplied in 100µl phosphate-buffered saline, 50% glycerol, 1 mg/ml BSA, and 0.05% sodium azide. (ecmbio.com)
  • PDPK1 stands for 3-phosphoinositide-dependent protein kinase 1. (wikipedia.org)
  • Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. (embl-heidelberg.de)