3 phosphoinositide dependent protein kinases. Medical search

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 2.7.1.37) 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 3.1.4.3), 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 2.7.1.107.

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 2.7.1.40.

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 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 ...

https://en.wikipedia.org/wiki/BX-912

"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 ...

https://en.wikipedia.org/wiki/GRB14

... 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 ... The degradation of Aux/IAA frees ARF proteins, which are then able to activate or repress genes at whose promoters they are ...

https://en.wikipedia.org/wiki/Auxin

... 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 ... This process requires modification of the auxin transporters (PIN proteins).[20] Flowering[edit]. Auxin plays also a minor role ...

https://en.wikipedia.org/wiki/Rooting_hormone

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 ...

https://en.wikipedia.org/wiki/Eisosome

... 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 ...

https://en.wikipedia.org/wiki/Mir-375

... 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 ...

https://en.wikipedia.org/wiki/Phosphatidylinositol_3,4-bisphosphate

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 ...

https://en.wikipedia.org/wiki/Sphingolipid

"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): ...

https://en.wikipedia.org/wiki/BIM-1

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 ...

https://en.wikipedia.org/wiki/Polar_auxin_transport

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 ...

https://en.wikipedia.org/wiki/Sodium-hydrogen_exchange_regulatory_cofactor_2

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 ... "Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and ... 1994). "Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A ...

https://tr.wikipedia.org/wiki/Majör_bazik_protein

... 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 ...

https://en.wikipedia.org/wiki/Protein_kinase_N1

... 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 ... Protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in ... The consensus sequence of protein kinase C enzymes is similar to that of protein kinase A, since it contains basic amino acids ...

https://en.wikipedia.org/wiki/Protein_kinase_C

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 ...

https://en.wikipedia.org/wiki/AKT3

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 ...

https://en.wikipedia.org/wiki/PRKCI

... 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 ...

https://en.wikipedia.org/wiki/Phosphoinositide-dependent_kinase-1

"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. ...

https://en.wikipedia.org/wiki/Protein_kinase_C_zeta_type

"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 ...

https://en.wikipedia.org/wiki/Integrin-linked_kinase

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. ...

https://en.wikipedia.org/wiki/AKT2

... protein kinase B)/glycogen synthase kinase-3 signaling pathway via phosphatidylinositol 3-kinase". Journal of Immunology. 163 ( ... Additionally, inhibition of PDK2 subsequently inhibits HIF1A in cancer cells by both a prolyl-hydroxylase (PHD)-dependent ... "Structure of pyruvate dehydrogenase kinase. Novel folding pattern for a serine protein kinase". The Journal of Biological ... PDK2 is an isozyme of pyruvate dehydrogenase kinase. The protein encoded by the PDK2 gene has two sites, an active site and an ...

https://en.wikipedia.org/wiki/PDK2

NIMA-related kinases (NEKs) are a group of protein kinases that are homologous to NIMA. Evidence suggests that NEKs perform ... "Identification and characterization of Nek6 protein kinase, a potential human homolog of NIMA histone H3 kinase". Biochem. ... Serine/threonine-protein kinase Nek6 is an enzyme that in humans is encoded by the NEK6 gene. The Aspergillus nidulans 'never ... It is a protein kinase which plays an important role in mitotic cell cycle progression. Required for chromosome segregation at ...

https://en.wikipedia.org/wiki/NEK6

Lizcano JM, Morrice N, Cohen P (2001). "Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a ... a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase ... This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine and threonine kinases. This kinase contains 2 non- ... Ribosomal protein S6 kinase alpha-2 is an enzyme that in humans is encoded by the RPS6KA2 gene. ...

https://en.wikipedia.org/wiki/RPS6KA2

5-trisphosphate-dependent activation of protein kinase B". Science. 279 (5351): 710-4. Bibcode:1998Sci...279..710S. doi:10.1126 ... "Carboxyl-terminal region conserved among phosphoinositide-kinase-related kinases is indispensable for mTOR function in vivo and ... and protein kinase C α (PKCα). mTORC2 also phosphorylates the serine/threonine protein kinase Akt/PKB on serine residue Ser473 ... "Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of ...

https://en.wikipedia.org/wiki/MTOR

They - in parallel with Dario Alessi - identified phosphoinositide-dependent kinase-1 as the PtdIns(3,4,5)P3-activated link ... 5-Trisphosphate-Dependent Activation of Protein Kinase B.". Science. 279 (5351): 710-714. Bibcode:1998Sci...279..710S. doi: ... "Protein Kinase B Kinases That Mediate Phosphatidylinositol 3,4, ... 5-trisphosphate in the activation of protein kinase B". Science ... between PI3K-1 activation and protein kinase B activation, a key pathway through which PtdIns(3,4,5)P3 formation regulates cell ...

https://en.wikipedia.org/wiki/Leonard_R._Stephens

They - in parallel with Dario Alessi - identified phosphoinositide-dependent kinase-1 as the PtdIns(3,4,5)P3-activated link ... 5-Trisphosphate-Dependent Activation of Protein Kinase B. Science 279, 710-714 Phill Hawkins' group at the Babraham Institute. ... Protein Kinase B Kinases That Mediate Phosphatidylinositol 3,4, ... 5-trisphosphate in the Activation of Protein Kinase B. Science ... between PI3K-1 activation and protein kinase B activation, a key pathway through which PtdIns(3,4,5)P3 formation regulates cell ...

https://en.wikipedia.org/wiki/Phillip_Thomas_Hawkins

... phosphoinositide dependent kinase 1 (PDPK1 at threonine 308) and the mammalian target of rapamycin complex 2 (mTORC2 at serine ... 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 a serine/threonine-specific protein kinase that plays a key role in multiple ... Yang ZZ, Tschopp O, Baudry A, Dümmler B, Hynx D, Hemmings BA (April 2004). "Physiological functions of protein kinase B/Akt". ...

https://en.wikipedia.org/wiki/Protein_kinase_B

... a protein kinase-dependent activator of tyrosine and tryptophan hydroxylases". Proceedings of the National Academy of Sciences ... Phosphoinositide-dependent kinase-1, RIMS1, RIMS2, TLX2, TNFAIP3, and ZFP36. GRCh38: Ensembl release 89: ENSG00000128245 - ... A member of a protein family that has been involved in the protein kinase C signalling pathway". Journal of Molecular Biology. ... This highly conserved protein family is found in both plants and mammals, and this protein is 99% identical to the mouse, rat ...

https://en.wikipedia.org/wiki/YWHAH

... 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. " ...

https://en.wikipedia.org/wiki/S1PR1

"Tobacco components stimulate Akt-dependent proliferation and NFkappaB-dependent survival in lung cancer cells". Carcinogenesis ... The phosphoinositide 3-kinase (PI3K/Akt) pathway is also an important contributor to NNK-induced cellular transformations and ... The ERK1/2 and Akt pathways show consequential changes in levels of protein expression as a result of NNK-activation in the ... NNK activates µ en m-calpain kinase which induce lung metastasis via the ERK1/2 pathway. This pathway upregulate cellular ...

https://en.wikipedia.org/wiki/NNK

P binding protein of the WIPI (WD-repeat protein interacting with phosphoinositides) protein family, was recently shown to ... E. Y. Chan, 'Regulation and Function of Uncoordinated-51 Like Kinase Proteins', Antioxid Redox Signal, 17 (2012), 775-85 ... This is directly related to the growth of cancer cells in a dose-dependent manner as well.[84][87] This data supports the ... Without efficient autophagy, neurons gather ubiquitinated protein aggregates and degrade. Ubiquitinated proteins are proteins ...

https://en.wikipedia.org/wiki/Autophagy_

P binding protein of the WIPI (WD-repeat protein interacting with phosphoinositides) protein family, was recently shown to ... "Regulation and Function of Uncoordinated-51 Like Kinase Proteins". Antioxidants & Redox Signaling. 17 (5): 775-785. doi:10.1089 ... This is directly related to the growth of cancer cells in a dose-dependent manner as well.[93][96] This data supports the ... Without efficient autophagy, neurons gather ubiquitinated protein aggregates and degrade. Ubiquitinated proteins are proteins ...

https://en.wikipedia.org/wiki/Autophagy

PA acts as a signaling lipid, recruiting cytosolic proteins to appropriate membranes (e.g., sphingosine kinase 1[8]). ... labeled phosphoinositides.[19] The addition of DAGK inhibitors eliminates the production of [32P]-labeled PA but not the PLD- ... The curvature induced by these lipids was shown to be dependent not only on the structure of lysoPA versus PA but also on ... anchored proteins: GPI-anchored proteins in liposomes and cells show similar behavior". Proceedings of the National Academy of ...

https://en.wikipedia.org/wiki/Phosphatidic_acid

Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... GTP-binding protein regulators regulate G proteins in several different ways. Small GTPases act as molecular switches in ... and thus requires another class of regulatory proteins to accelerate this activity, the GTPase activating proteins (GAPs). ... GTP-Binding+Protein+Regulators at the US National Library of Medicine Medical Subject Headings (MeSH) ...

https://en.wikipedia.org/wiki/GTP-binding_protein_regulators

protein kinase activity. • JUN kinase binding. • non-membrane spanning protein tyrosine kinase activity. • transferase activity ... "Integrin-dependent translocation of phosphoinositide 3-kinase to the cytoskeleton of thrombin-activated platelets involves ... protein tyrosine kinase activity. • protein phosphatase binding. 細胞の構成要素. • 細胞質. • 細胞質基質. • 膜. • 焦点接着. • extrinsic component of ... FAK（focal adhesion kinase、フォーカルアドヒージョンキナーゼ、焦点接着キナーゼ、接着斑

https://ja.wikipedia.org/wiki/FAK

protein serine/threonine kinase activity. • GO:0001948 protein binding. • insulin receptor substrate binding. • ATP binding. • ... Foster FM, Traer CJ, Abraham SM, Fry MJ (August 2003). "The phosphoinositide (PI) 3-kinase family". Journal of Cell Science. ... Sade H, Krishna S, Sarin A (January 2004). "The anti-apoptotic effect of Notch-1 requires p56lck-dependent, Akt/PKB-mediated ... G-protein coupled receptor signaling pathway. • positive regulation of protein kinase B signaling. • phosphatidylinositol 3- ...

https://en.wikipedia.org/wiki/PIK3CA

This approach was used to characterize the substrate specificity of a large number of protein kinases. The kinase specificity ... and colleagues demonstrated that a kinase activity associated with the middle T oncoprotein is a phosphoinositide kinase,[7] ... Auger KR, Serunian LA, Soltoff SP, Libby P, Cantley LC (April 1989). "PDGF-dependent tyrosine phosphorylation stimulates ... October 2004). "A rapid method for determining protein kinase phosphorylation specificity". Nat. Methods. 1 (1): 27-9. doi: ...

https://en.wikipedia.org/wiki/Lewis_C._Cantley

Phosphoinositide 3-kinase. References[edit]. *Stein RC( 2001) Prospects for phosphoinositide 3-kinase inhibition as a cancer ... 2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... Foster FM, Traer CJ, Abraham SM, and Fry MJ (2003) The phosphoinositide (PI) 3-kinase family J Cell Sci 116:3037-3040.[2] ... Vanhaesebroeck B, Waterfield MD.(1999) Signaling by distinct classes of phosphoinositide 3-kinases. Exp Cell Res. 253(1):239-54 ...

https://en.wikipedia.org/wiki/Class_II_PI_3-kinases

Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... protein complex binding. • signal transducer activity. • protein binding. • GTPase activity. • GTPase binding. • G-protein ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... protein heterotrimerization. • Wnt signaling pathway, calcium modulating pathway. • protein folding. • G-protein coupled ...

https://en.wikipedia.org/wiki/GNB1

CRBN: Cereblon protein[12]. *DCLK3: Doublecortin like kinase 3. *EAF1: ELL associated factor 1 ... PIK3CA: phosphoinositide-3-kinase, catalytic, alpha polypeptide. *PROSER1: Proline and serine rich protein 1 ... CACNA2D3: calcium channel, voltage-dependent, alpha 2/delta subunit 3. *CCR5: chemokine (C-C motif) receptor 5 ... ZBED2: encoding protein Zinc finger BED-type containing 2. *ZNF9: zinc finger protein 9 (a cellular retroviral nucleic acid ...

https://en.wikipedia.org/wiki/Chromosome_3_(human)

protein phosphorylation. • negative regulation of cytokine production. • MyD88-dependent toll-like receptor signaling pathway. ... Carpenter CL (2004). "Btk-dependent regulation of phosphoinositide synthesis". Biochem. Soc. Trans. 32 (Pt 2): 326-9. doi: ... non-membrane spanning protein tyrosine kinase activity. • ATP binding. • protein binding. • protein tyrosine kinase activity. ... identical protein binding. • protein kinase activity. • transferase activity. • kinase activity. • phosphatidylinositol-3,4,5- ...

https://en.wikipedia.org/wiki/Bruton's_tyrosine_kinase

Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Types of G protein signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ... G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... Heterotrimeric G proteins[edit]. Main article: Heterotrimeric G proteins. Different types of heterotrimeric G proteins share a ...

https://en.wikipedia.org/wiki/G-proteins

2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... the RNA-polymerization activity of PNPase was initially believed to be responsible for DNA-dependent synthesis of messenger RNA ... The protein is present in bacteria and in the chloroplasts[2] and mitochondria[7] of some eukaryotic cells. In eukaryotes and ... In its active form, the protein forms a ring structure consisting of three PNPase molecules. Each PNPase molecule consists of ...

https://en.wikipedia.org/wiki/Polynucleotide_phosphorylase

Phosphorylation by cAMP-dependent protein kinasesEdit. Cyclic AMP-dependent protein kinases (protein kinase A) are activated by ... along with some phosphoinositide-3-kinase (PI3K) isoforms. G-protein-independent signalingEdit. Although they are classically ... The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs.[53] G-protein-coupled ... stimulative regulative G-protein (Gs) or inhibitory regulative G-protein (Gi); adenylyl cyclase; protein kinase A (PKA); and ...

https://en.m.wikipedia.org/wiki/G_protein-coupled_receptors

Protein kinase C, phosphoinositide 3-kinase, and phospholipase C (PLC) are all needed for signalling and controlling particle ... Dupuy, A. G.; Caron, E. (6 May 2008). "Integrin-dependent phagocytosis - spreading from microadhesion to new concepts". Journal ... Role of Lipopolysaccharide in Cell Invasion and in Activation of the Mitogen-Activated Protein Kinase ERK". Infection and ... creating a more hostile environment for pathogens and facilitating protein degradation. The bacterial proteins are denatured in ...

https://en.m.wikipedia.org/wiki/Phagosome

2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... Other names in common use include pyrimidine ribonucleoside kinase, uridine-cytidine kinase, uridine kinase (phosphorylating), ... I. Uridine-cytidine kinase of Novikoff ascites rat tumor". The Journal of Biological Chemistry. 244 (8): 2204-9. PMID 5782006. ... In enzymology, an uridine kinase (EC 2.7.1.48) is an enzyme that catalyzes the chemical reaction ...

https://en.wikipedia.org/wiki/Uridine_kinase

Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... Guanylyl cyclase activator (protein). References[edit]. *^ Sakurai K.; Chen J.; Kefalov V. (2011). "Role of guanylate cylcase ... Guanylate cyclase is often part of the G protein signaling cascade that is activated by low intracellular calcium levels and ... Depending on cell type, it can drive adaptive/developmental changes requiring protein synthesis. In smooth muscle, cGMP is the ...

https://en.wikipedia.org/wiki/Guanylate_cyclase

"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 Rho GTPases and are ... Protein Azurophilic granules (or "primary granules"). Myeloperoxidase, bactericidal/permeability-increasing protein (BPI), ...

https://en.wikipedia.org/wiki/Neutrophil_granulocyte

... cyclin-dependent kinase and DREAM complex. When it is time for a cell to enter S phase, complexes of cyclin-dependent kinases ( ... "The N-Terminal 24 Amino Acids of the p55 Gamma Regulatory Subunit of Phosphoinositide 3-Kinase Binds Rb and Induces Cell Cycle ... negative regulation of protein serine/threonine kinase activity. • negative regulation of tau-protein kinase activity. • ... kinase binding. • protein binding. • androgen receptor binding. • identical protein binding. • enzyme binding. • ubiquitin ...

https://en.m.wikipedia.org/wiki/Retinoblastoma_protein

de 1997). «Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase». Proc. Natl. Acad. Sci. ... de 2001). «p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human ... de 2000). «Stress-induced activation of protein kinase CK2 by direct interaction with p38 mitogen-activated protein kinase». J ... Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase ...

https://es.wikipedia.org/wiki/MAPK14

... nuclear located protein kinase C and cyclic AMP-dependent protein kinase". Frontiers in Bioscience. 13 (13): 1206-26. doi: ... involved in calcium-mediated activation of protein kinase C;[76] the prostaglandins, which are one type of fatty-acid derived ... Protein-lipid interaction. *Phenolic lipid, a class of natural products composed of long aliphatic chains and phenolic rings ... Parodi AJ, Leloir LF (April 1979). "The role of lipid intermediates in the glycosylation of proteins in the eucaryotic cell". ...

https://en.wikipedia.org/wiki/Lipid

... function of cAMP-dependent protein kinase. In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein ... an enzyme called protein kinase A (PKA).[12]. The PKA enzyme is also known as cAMP-dependent enzyme because it gets activated ... "Multiple pathway signal transduction by the cAMP-dependent protein kinase". FASEB J. 8 (15): 1227-36. doi:10.1096/fasebj.8.15. ... "Signal transduction through the cAMP-dependent protein kinase". Mol. Cell. Biochem. 127-128: 179-86. doi:10.1007/BF01076769. ...

https://en.wikipedia.org/wiki/CAMP-dependent_pathway

... s, when bound with the dependent kinases, such as the p34/cdc2/cdk1 protein, form the maturation-promoting factor. MPFs ... Cyclin-dependent kinase inhibitor protein. *Cyclin-dependent kinase. *Cyclin. Lipid. *Phosphoinositide phospholipase C ... is a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (CDK ... Nurse won the 2001 Nobel Prize in Physiology or Medicine for their discovery of cyclin and cyclin-dependent kinase.[17] ...

https://en.wikipedia.org/wiki/Cyclin

2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... This enzyme is also called galacturonokinase (phosphorylating) D-galacturonic acid kinase. This enzyme participates in ... RNA-dependent RNA polymerase. Polyadenylation. PAP. PNPase. Phosphorolytic. 3' to 5' exoribonuclease. *RNase PH ... Phosphoinositide 3 *Class I PI 3. *Class II PI 3. *Sphingosine. *Glucose-1,6-bisphosphate synthase ...

https://en.wikipedia.org/wiki/Galacturonokinase

"Definition of a metal-dependent/Li+-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core ... It is known with good certainty that signals from the receptors coupled to the phosphoinositide signal transduction is affected ... Gould, Todd; Picchini, Alyssa; Einat, Haim; Manji, Husseini (2006-11-01). "Targeting Glycogen Synthase Kinase-3 in the CNS: ... Dopamine and G-protein couplingEdit. During mania, there is an increase in neurotransmission of dopamine that causes a ...

https://en.m.wikipedia.org/wiki/Lithium_

2.7.10-2.7.13: protein kinase. (PO4; protein acceptor). 2.7.10: protein-tyrosine. *see tyrosine kinases ... Protein domain[edit]. Function[edit]. In molecular biology, this protein domain, Taq polymerase exonuclease, refers to a domain ... 127 (3): 1550-7. PMC 232952 . PMID 8432.. *^ a b Saiki, RK; et al. (1988). "Primer-directed enzymatic amplification of DNA with ... as an enzyme able to withstand the protein-denaturing conditions (high temperature) required during PCR.[2] Therefore, it ...

https://en.wikipedia.org/wiki/Taq_polymerase

PCr generated by mtCK in mitochondria is shuttled to cytosolic CK that is coupled to ATP-dependent processes, e.g. ATPases, ... A number of genuine CK structures have been solved by high-resolution electron microscopy and protein X-ray crystallography by ... Creatine kinase (CK), also known as creatine phosphokinase (CPK) or phosphocreatine kinase, is an enzyme (EC 2.7.3.2) expressed ... Creatine kinase in the blood may be high in health and disease. Exercise increases the outflow of creatine kinase to the blood ...

https://en.wikipedia.org/wiki/Creatine_kinase

5-bisphosphate to calcium-dependent activator protein for secretion (CAPS), a potential phosphoinositide effector protein for ... dependent secretion by protein kinase C.". J. Biol. Chem. 267 (33): 23972-81. PMID 1429734. الوسيط ,السنة=. تم تجاهله (مساعدة ... "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of ... 2004). "A family of Ca2+-dependent activator proteins for secretion: comparative analysis of structure, expression, ...

https://ar.wikipedia.org/wiki/CADPS

P3-dependent protein kinase-1 (PDK1). None of the inositol phospholipids tested activated or inhibited PKBalpha or induced its ... Protein kinase B (PKB), also known as c-Akt, is activated rapidly when mammalian cells are stimulated with insulin and growth ... CONLCUSIONS: PDK1 is likely to be one of the protein kinases that mediate the activation of PKB by insulin and growth factors. ... We have purified 500 000-fold from rabbit skeletal muscle extracts a protein kinase which phosphorylates PKBalpha at Thr308 and ...

https://www.ncbi.nlm.nih.gov/pubmed/9094314?dopt=Abstract

The activation of protein kinase B (PKB, also known as c-Akt) is stimulated by insulin or growth factors and results from its ... We recently identified a protein kinase, termed PDK1, that phosphorylates PKB at Thr308 only in the presence of lipid vesicles ... Human PDK1 is homologous to the Drosophila protein kinase DSTPK61, which has been implicated in the regulation of sex ... PKB and PKC subfamily of protein kinases and a carboxy-terminal pleckstrin homology (PH) domain. The PDK1 gene is located on ...

https://www.ncbi.nlm.nih.gov/pubmed/9368760?dopt=Abstract

We tested the kinase in the presence of several inositol phospholipids and found that only low micromolar concentrations of the ... We have purified 500 000-fold from rabbit skeletal muscle extracts a protein kinase which phosphorylates PKBalpha at Thr308 and ... P3-dependent protein kinase-1 (PDK1). None of the inositol phospholipids tested activated or inhibited PKBalpha or induced its ... Background: Protein kinase B (PKB), also known as c-Akt, is activated rapidly when mammalian cells are stimulated with insulin ...

https://pubmed.ncbi.nlm.nih.gov/9094314/?dopt=Abstract

Protein target information for Chain A, 3-phosphoinositide-dependent protein kinase 1 (human). Find diseases associated with ...

https://pubchem.ncbi.nlm.nih.gov/protein/3QC4_A

Inhibition of PDPK-1-dependent kinases, such as P70-S6K, but not others, such as mTORC-1, stimulated rod development. The P70- ... or mTORC2-dependent increase in rods. Together the data indicate that PDPK-1 and other intrinsic kinases downstream of IGF-1 ... We also found that inhibition of the kinase mTORC-2, also stimulated by insulin activity, similarly increased rod formation, ... S6K-dependent increase in rods appears to be correlated with phosphorylation of Thr252 and not at Thr389, a substrate of mTORC- ...

https://www.selleckchem.com/blog/The-3-Phosphoinositide-Dependent-Protein-Kinase-1-Inhibits-Rod-Photoreceptor-Development.html?pathway=logical_nf-kb-pathway

Activation of cGMP-dependent protein kinase by protein kinase C. J. Biol. Chem. 278: 16706-16712. ... Nitric oxide activation of p38 mitogen-activated protein kinase in 293T fibroblasts requires cGMP-dependent protein kinase. J. ... K-252 compounds, novel and potent inhibitors of protein kinase C and cyclic nucleotide-dependent protein kinases. Biochem. ... SNAP receptor protein; t-SNARE, target membrane SNARE; PLC, phospholipase C; PKC, protein kinase C; PKG, cGMP-dependent protein ...

https://www.jimmunol.org/content/178/1/416

... kinase (e.g., LY294002; Ref. 27 ), protein kinase C (staurosporine; Ref. 28 ), cyclin-dependent kinases (29) , and vascular ... Tsichlis PN AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent ... phosphoinositide-dependent protein kinase-1. J Biol Chem, 275: 40400-6, 2000. ... phosphoinositide-dependent kinase-1 (PDK-1) in PI 3- kinase signaling. Front Biosci, 7: d886-902, 2002. ...

https://cancerres.aacrjournals.org/content/64/12/4309?ijkey=a99415953fe3d0f230442ab81bf0342033226b11&keytype2=tf_ipsecsha

Activation of protein kinase B β and γ isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in ... comparison with protein kinase B α. Kay S. WALKER, Maria DEAK, Andrew PATERSON, Kevin HUDSON, Philip COHEN, Dario R. ALESSI ... Activation of protein kinase B β and γ isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in ... Activation of protein kinase B β and γ isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in ...

http://www.biochemj.org/content/331/1/299

3-phosphoinositide dependent protein kinase 1 - PDK1 family. Detailed annotation on the structure, function, physiology, ... Phosphoinositide-dependent protein kinase 1 (PDK1) mediates potent inhibitory effects on eosinophils. Eur. J. Immunol., 45 (5 ... PkB kinase , protein kinase B kinase , 3-phosphoinositide dependent protein kinase-1 ... 2010) Molecular pharmacology and antitumor activity of PHT-427, a novel Akt/phosphatidylinositide-dependent protein kinase 1 ...

http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1519

... is a protein kinase that phosphorylates and activates several other protein kinases from the AGC group (which includes PKA, PKG ... Phosphoinositide-dependent protein kinase 1 (PDK1) is a protein kinase that phosphorylates and activates several other protein ... Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation Trends Biochem Sci. 2004 Mar;29(3):136-42. doi: ... interact with and phosphorylate specific substrate conformations and thus sets PDK1 at the centre of a protein conformation ...

https://pubmed.ncbi.nlm.nih.gov/15003271/

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 ...

https://en.wikipedia.org/wiki/Phosphoinositide-dependent_kinase-1

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- ...

https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-6-77

D. E. Heppner and A. van der Vliet, "Redox-dependent regulation of epidermal growth factor receptor signaling," Redox Biology, ... MI-1 was synthesized as protein kinases inhibitor [8]. It was tested on 32 protein kinases for determination of inhibitory ... Anti-Inflammatory Effects of Protein Kinase Inhibitor Pyrrol Derivate. Halyna M. Kuznietsova, Maryna S. Yena, Iryna P. Kotlyar ... Protein kinase inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1Н-pyrrol-2,5-dione (MI-1) (Figure 1) has been ...

https://www.hindawi.com/journals/tswj/2016/2145753/

Sequence domains: Protein kinase domain Structure domains: * Phosphorylase Kinase; domain 1 * Transferase(Phosphotransferase) ... Protein kinase, ATP binding site * Occurring in:. *3-phosphoinositide-dependent protein kinase 1. > Serine/threonine-protein ... Protein kinase domain * Occurring in:. *3-phosphoinositide-dependent protein kinase 1. > ... 3-phosphoinositide-dependent protein kinase 1 Chain: A Molecule details › Chain: A. Length: 310 amino acids. Theoretical weight ...

http://www.ebi.ac.uk/pdbe/entry/pdb/1oky

... protein kinase A; PKB/Akt: protein kinase B; ERK: extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; FAK: ... extracellular signal-regulated kinase; JNK: c-Jun N-terminal kinase; FAK: focal adhesion kinase; PI3K: phosphoinositide-3 ... α0 subunits can in turn inhibit voltage dependent Ca2+ channels contributing to the inhibition of membrane depolarization. βγ ... protein kinase A; PKB/Akt: protein kinase B; ERK: ... α0 subunits can in turn inhibit voltage dependent Ca2+ channels ...

https://www.mdpi.com/2076-3425/3/3/1043/htm

... triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates ... triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates ... triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates ... triphosphate binding to phosphoinositide-dependent kinase 1 regulates a protein kinase B/Akt signaling threshold that dictates ...

https://discovery.dundee.ac.uk/en/publications/phosphoinositide-345-triphosphate-binding-to-phosphoinositide-dep

Phosphorylation and activation of PINOID by the phospholipid signaling kinase 3-phosphoinositide-dependent protein kinase 1 ( ... Phosphorylation and activation of PINOID by the phospholipid signaling kinase 3-phosphoinositide-dependent protein kinase 1 ( ...

https://pure.royalholloway.ac.uk/portal/en/publications/phosphorylation-and-activation-of-pinoid-by-the-phospholipid-signaling-kinase-3phosphoinositidedependent-protein-kinase-1-pdk1-in-arabidopsis

... p65 protein expression in a dose-dependent manner (Figure 4B). Note that NAC had no effect on p50 protein (Figure 4B). ... protein kinase-1 regulates proliferation and survival of cancer cells with an activated mitogen-activated protein kinase ... As shown in Figure 2A-B, NAC induced PPARα protein expression in a dose- and time-dependent manner with a maximal induction ... Cells exposed to NAC resulted in significant decrease in PDK1 protein expression in a dose- and time-dependent manner with ...

https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-32-43

The protein kinase ATM is a sensor for reactive oxygen species.. *Abstract ... Online Cover This week features a Research Article that identifies ARAP3 as the downstream effector of phosphoinositide 3- ... Intrinsic differences in mTORC2-dependent Akt activation underlie the region-specific effects of neurofibromatosis-1 on glial ... Membrane fusion proteins cooperate to promote rapid secretory vesicle exocytosis from neuroendocrine cells. ...

http://stke.sciencemag.org/content/3/145

Previous work described an allosteric site mediating phosphorylation-dependent activation of AGC kinases. The AGC kinase PDK1 ... Structure and allosteric effects of low-molecular-weight activators on the protein kinase PDK1.. Hindie, V., Stroba, A., Zhang ... Previous work described an allosteric site mediating phosphorylation-dependent activation of AGC kinases ... ... Crystal structure of a mutant of human PDK1 Kinase domain in complex with ATP. *DOI: 10.2210/pdb3HRC/pdb ...

https://www.rcsb.org/structure/3HRC

Specificity analysis with a panel of 29 protein kinases reveals that these bisindolyl maleimide inhibitors also inhibit PDK1, a ... nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific inhibitor, is in clinical trials against diabetes and ... nanomolar protein kinase C inhibitors. LY333531, a PKCbeta-specific inhibitor, is in clinical trials against diabetes and ... Structure of human PDK1 kinase domain in complex with BIM-3. *DOI: 10.2210/pdb1UU9/pdb ...

https://www.rcsb.org/structure/1UU9

PIK3R5 and its membrane recruitment and beta-gamma G protein dimer-dependent activation requires HRAS bound to PIK3CG. Recruits ... The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G proteins than PIK3CG: ... Acts as an adapter to drive activation of PIK3CG by beta-gamma G protein dimers. ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ...

https://www.uniprot.org/uniprot/Q3U6Q4

We further hypothesize that insulin-activated PI3-kinase pathway and inflammatory signaling mediated by several I,i,κ,/i,B ... kinases may constitute negative feedback leading to insulin resistance at least in the fat tissue. Finally, we discuss ... as compared to inactivating mutations in insulin receptor or signaling proteins that occur relatively rare. Here, we argue that ... phosphoinositide-dependent kinase; S6K: ribosomal protein S6 kinase. According to Boucher et al. [15], with changes. ...

https://www.hindawi.com/journals/ije/2017/5076732/

... cAMP-dependent or cGMP-dependent protein kinases and protein kinase C; UCN-01, 7-hydroxystaurosporine; LY294002, 2-(4- ... Differential Roles of Phosphoinositide-Dependent Protein Kinase-1 and Akt1 Expression and Phosphorylation in Breast Cancer Cell ... Differential Roles of Phosphoinositide-Dependent Protein Kinase-1 and Akt1 Expression and Phosphorylation in Breast Cancer Cell ... Differential Roles of Phosphoinositide-Dependent Protein Kinase-1 and Akt1 Expression and Phosphorylation in Breast Cancer Cell ...

https://molpharm.aspetjournals.org/content/70/3/1045

Ahmad KA, Harris NH, Johnson AD, Lindvall HC, Wang G, Ahmed K. Protein kinase CK2 modulates apoptosis induced by resveratrol ... Imai S, Armstrong CM, Kaeberlein M, Guarente L. Transcriptional silencing and longevity protein Sir2 is an NAD-dependent ... Zschoernig B, Mahlknecht U. Carboxy-terminal phosphorylation of SIRT1 by protein kinase CK2. Biochem Biophys Res Commun. 2009; ... dependent Sir2 histone/protein deacetylases. Proc Natl Acad Sci U S A. 2004;101:8563-8.PubMedPubMedCentralGoogle Scholar ...

https://link.springer.com/article/10.1007/s13277-015-3488-x

Required for G protein-mediated activation of PIK3CG (By similarity). ... Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. ... Translocated to the plasma membrane in a beta-gamma G protein-dependent manner.By similarity. Manual assertion inferred from ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ...

https://www.uniprot.org/uniprot/Q8WYR1

... belongs to the family of NLR proteins. Upon activation NALP3 assembles with the adaptor protein ASC to form a protein-complex ... operates in cells in response to phosphoinositide 3-kinase activation and phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4, ... Aurora Kinases as Druggable Targets in Cancer Therapy » GLAST Menu Not Found. Skip to content *Home ... 3-Phosphoinositide-dependent protein kinase 1 (PDK1) operates in cells in response to. 3-Phosphoinositide-dependent protein ...

http://www.exposed-skin-care.net/2016/07/05/background-neutrophils-are-key-players-in-the-innate-host-defense-and-their/

Protein-tyrosine phosphatase Shp-1 is a negative regulator of IL-4- and IL-13-dependent signal transduction. J. Biol. Chem. 273 ... Src family protein-tyrosine kinases alter the function of PTEN to regulate phosphatidylinositol 3-kinase/AKT cascades. J. Biol ... Functionally, the ability of SHP-1 to inhibit CCR7 signaling and protein upregulation resulted in reduced CCL21-dependent BMDC ... Downstream of TLR4, SHP-1 showed increased interaction with several proteins including IL-1R-associated kinase-4, and modulated ...

http://www.jimmunol.org/content/186/7/3934.full

2003 May;3(2):173-7 Detailed expression data for these assays: 27 results Indicates gene expression was analyzed but not ...

http://www.informatics.jax.org/gxdlit/key/31280

... activating redox-sensitive protein kinases, such as JAKs, PKC, PI3K, and PDK; (2) activating mitogen-activated protein kinase ( ... These pathways are also likely dependent on the stimulus and cell type [44], and as mentioned above, Ang II has been shown to ... serine/threonine protein kinase; PKC: protein kinase C; PDK: 3-phosphoinositide-dependent kinase; Erk1/2: extracellular signal- ... and may activate a large variety of protein kinases, such as MAPK, tyrosine kinases, and Rho kinases, and transcription factors ...

https://www.intechopen.com/books/reactive-oxygen-species-ros-in-living-cells/reactive-oxygen-species-at-high-altitude-hypobaric-hypoxia-on-the-cardiovascular-system

We tested the kinase in the presence of several inositol phospholipids and found that only low micromolar concentrations of the D enantiomers of either phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3) or PtdIns(3,4)P2 were effective in potently activating the kinase, which has been named PtdIns(3,4,5)P3-dependent protein kinase-1 (PDK1). (nih.gov)
PDK1 activity was not affected by wortmannin, indicating that it is not likely to be a member of the phosphoinositide 3-kinase family. (nih.gov)
CONLCUSIONS: PDK1 is likely to be one of the protein kinases that mediate the activation of PKB by insulin and growth factors. (nih.gov)
PDK1 may, therefore, play a key role in mediating many of the actions of the second messenger(s) PtdIns(3,4, 5)P3 and/or PtdIns(3,4)P2. (nih.gov)
3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase. (nih.gov)
We recently identified a protein kinase, termed PDK1, that phosphorylates PKB at Thr308 only in the presence of lipid vesicles containing phosphatidylinositol 3,4,5-trisphosphate (Ptdlns(3,4,5)P3) or phosphatidylinositol 3,4-bisphosphate (Ptdlns(3,4)P2). (nih.gov)
Human PDK1 is homologous to the Drosophila protein kinase DSTPK61, which has been implicated in the regulation of sex differentiation, oogenesis and spermatogenesis. (nih.gov)
Expressed PDK1 and DSTPK61 phosphorylated Thr308 of PKB alpha only in the presence of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2. (nih.gov)
Experiments in which the PH domains of either PDK1 or PKB alpha were deleted indicated that the binding of Ptdlns(3,4,5)P3 or Ptdlns(3,4)P2 to PKB alpha is required for phosphorylation and activation by PDK1. (nih.gov)
All three isoforms (PKBα, PKBβ and PKBγ) were phosphorylated at similar rates and activated to similar extents by 3-phosphoinositide-dependent protein kinase-1 (PDK1). (biochemj.org)
Phosphorylation and activation of each enzyme required the presence of PtdIns(3,4,5) P 3 or PtdIns(3,4) P 2 , as well as PDK1. (biochemj.org)
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. (nih.gov)
PDK1 has the ability to recognize, interact with and phosphorylate specific substrate conformations and thus sets PDK1 at the centre of a protein conformation sensor mechanism. (nih.gov)
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)
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)
The present study explored the consequences of phosphoinositide (3,4,5)-triphosphate [PI(3,4,5) P-3] binding to the pleckstrin homology (PH) domain of the serine/threonine kinase 3-phosphoinositide-dependent kinase 1 (PDK1). (dundee.ac.uk)
The salient finding is that PDK1 directly transduces the PI(3,4,5)P-3 signaling that determines T-cell trafficking programs but not T-cell growth and proliferation. (dundee.ac.uk)
However, a PDK1 mutant that cannot bind PI(3,4,5)P-3 cannot trigger the signals that terminate the expression of the transcription factor KLF2 in activated T cells and cannot switch the chemokine and adhesion receptor profile of naOve T cells to the profile of effector T cells. (dundee.ac.uk)
The PDK1 PH domain also is required for the maximal activation of Akt/protein kinase B (PKB) and for the maximal phosphorylation and inactivation of Foxo family transcription factors in T cells. (dundee.ac.uk)
PI(3,4,5)P-3 binding to PDK1 and the strength of PKB activity thus can dictate the nature of the T-cell response. (dundee.ac.uk)
While PPARα ligand enhanced, PPARα antagonist and siRNA abrogated the effect of NAC on PDK1 promoter activity, protein expression and cell growth. (biomedcentral.com)
Silencing of p53 and overexpression of p65 blocked the effect of NAC on PDK1 promoter activity and protein expression. (biomedcentral.com)
Our results show that NAC inhibits PDK1 expression through PPARα-mediated induction of p53 and inhibition of p65 protein expression. (biomedcentral.com)
The AGC kinase PDK1 is activated by the docking of a phosphorylated motif from substrates. (rcsb.org)
Altogether, we present molecular details of the allosteric changes induced by small compounds that trigger the activation of PDK1 through mimicry of phosphorylation-dependent conformational changes. (rcsb.org)
Specificity analysis with a panel of 29 protein kinases reveals that these bisindolyl maleimide inhibitors also inhibit PDK1, a key kinase from the insulin signaling pathway, albeit in the lower microM range. (rcsb.org)
To understand the molecular basis of inhibition, the PDK1 kinase domain was cocrystallized with these bisindolyl maleimide inhibitors. (rcsb.org)
3-Phosphoinositide-dependent protein kinase-1 (PDK1) and Akt1 are two closely related components of the phosphatidylinositol-3 kinase (PI3K) pathway, which is aberrantly regulated in breast cancer. (aspetjournals.org)
We further identify the 3-phosphoinositide-dependent protein kinase 1 (PDK1), a well-known kinase involved in the PI3K-Akt signaling pathway, as a direct Meis3 target, which mediates its role in β-cell survival. (biomedsearch.com)
The PI3K pathway that is stimulated by a wide range of tyrosine kinase growth factor receptors is the major activator of Akt signaling via stimulation of PDK1 that phosphorylates and activates Akt. (mcponline.org)
PI3K signaling crucially involves phosphoinositide-dependent protein kinase (PDK1). (uzh.ch)
Fragment screening of phosphoinositide-dependent kinase-1 (PDK1) in a biochemical kinase assay afforded hits that were characterized and prioritized based on ligand efficiency and binding interactions with PDK1 as determined by NMR. (proteopedia.org)
Well-defined structure-activity relationships and protein crystallography provide a basis for further elaboration and optimization of 19 as a PDK1 inhibitor. (proteopedia.org)
AKT activation requires phosphorylation of the activation loop (T308) by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and the hydrophobic motif (S473) by the mammalian target of rapamycin complex 2 (mTORC2). (pnas.org)
Phosphorylation of the activation loop T308 by 3-phosphoinositide-dependent protein kinase 1 (PDK1) is essential for AKT activation ( 8 ). (pnas.org)
The phosphoinositide 3-kinase/3-phosphoinositide-dependent kinase 1 (PDK1)/AKT signaling pathway plays a role in cancer cell growth, and tumor angiogenesis, and could be a new target for anti-cancer drugs. (wikipedia.org)
Of particular interest are the protein serine-threonine kinases Akt [also called protein kinase B (PKB)] and phosphoinositide-dependent kinase 1 (PDK1). (sciencemag.org)
Association with PI(3,4,5)P 3 at the membrane brings these proteins into proximity and facilitates phosphorylation of Akt by PDK1 ( 3 ). (sciencemag.org)
PI3K activates 3-phosphoinositide-dependent protein kinase 1 (PDK1), which activates Akt, a serine kinase. (genome.jp)
The Arabidopsis 3-phosphoinositide-dependent protein kinase (PDK1) could couple lipid signals to the activation of several protein kinases of the so-called AGC kinase family. (mendeley.com)
The Arabidopsis AGC kinases contain sequence motives required for the docking of PDK1 and phosphorylation of their activation loop in the kinase catalytic domain. (mendeley.com)
A recent study indicated that celecoxib derivatives such as OSU03013 induce apoptosis in prostate cancer cells through the 3-phosphoinositide-dependent kinase 1 (PDK1)/AKT signaling pathway and may more strongly inhibit cell growth than celecoxib ( 5 ). (aacrjournals.org)
PDK1 K465E/K465E PH domain knock-in mice express a form of PDK1 (with lysine 465 exchanged for glutamic acid) that is normally active, but unable to bind PtdIns(3,4,5) P 3 . (biologists.org)
Akt belongs to the AGC kinase family, and PDK1 activates other members of this family including S6K and SGK isoforms. (biologists.org)

These studies have further indicated that E4ORF1 bypasses IRS-1 or -2 signaling yet improves glucose disposal by upregulating the distal insulin signaling pathway that involves phosphatidylinositol 3-kinase (PI3K), AKT, and GLUT4 through Ras activation ( 8 ). (diabetesjournals.org)
However, the precise mechanism by which the PI 3-kinase-Akt signaling pathway transduces a survival signal that inhibits apoptosis is unknown. (sciencemag.org)
To determine whether BAD phosphorylation is regulated through the PI 3-kinase-Akt signaling pathway in vivo , IL-3-dependent FL5.12 lymphoid progenitor cells that coexpress Bcl-2 and BAD ( 12 ) were incubated with increasing concentrations of wortmannin and LY294002, two specific inhibitors of PI 3-kinase ( 5 , 10 , 11 ). (sciencemag.org)
The phosphatidylinositol 3-kinase (PI3K) signaling pathway is a conserved signal transduction cascade that is fundamental for the correct development of the nervous system. (biologists.org)
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)
The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines (1-3), and research investigators consider it an important target in the diagnosis and treatment of cancer (4). (cellsignal.com)

The serine/threonine kinase Akt is a key mediator of cell survival and cell growth that is activated by most growth factors, but its downstream signaling largely remains to be elucidated. (mcponline.org)
The serine/threonine kinase Akt/PKB 1 belongs to the cAMP-dependent protein kinase A/protein kinase G/protein kinase C (AGC) superfamily of protein kinases that share structural homology within their catalytic domain and have similar mechanisms of activation ( 1 ). (mcponline.org)
Although no single critical Akt substrate for tumor development and maintenance has been identified, perhaps the best studied downstream substrate is the serine/threonine kinase, mTOR. (aacrjournals.org)
Non-specific serine/threonine protein kinase. (cathdb.info)
This is a heterogeneous group of serine/threonine protein kinases that do not have an activating compound and are either non-specific or their specificity has not been analyzed to date. (cathdb.info)
Various signaling proteins, including protein serine-threonine kinases, protein tyrosine kinases, and exchange factors that regulate heterotrimeric guanosine triphosphate (GTP)-binding proteins (G proteins), have domains that specifically bind to D-3 phosphorylated phosphoinositides. (sciencemag.org)
The key regulator of the PI3K/Akt pathway is Akt/PKB, a family of three closely related serine/threonine-protein kinases. (antibodies-online.com)
The serine-threonine protein kinase encoded by the AKT1 gene is catalytically inactive in serum-starved primary and immortalized fibroblasts. (antibodies-online.com)
Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase-dependent manner. (sciencemag.org)
BAD resides in the cytosol and is phosphorylated on serine residues after cells are stimulated with IL-3 ( 3 ). (sciencemag.org)
PI 3-kinase phosphorylates inositol lipids that act as second messengers for several targets, including the serine-threonine Akt kinase ( 6 , 7 , 8 ). (sciencemag.org)
The signals downstream of PI3K are still unknown, and there is controversy as to whether the serine/threonine kinase Akt/protein kinase B (PKB) ( 6 , 7 ) or the protein kinase C (PKC) isoform λ/ζ ( 8 ) mediates insulin stimulation of glucose transport. (jci.org)
mTOR is a serine-threonine kinase with lipid kinase activity. (aacrjournals.org)
Eight mammalian PI3-Ks are divided into three main classes: class I PI3-Ks phosphorylate membrane phosphatidylinositol to give PI(3, 4, 5)P 3 that recruits the cytoplasmic serine/threonine kinase Akt by binding to its pleckstrin homology domain. (aacrjournals.org)
Because phosphoinositide-dependent protein kinase-1 phosphorylates Akt1 kinase only on Thr-308 ( 2 ), an additional, so far unknown, serine kinase is believed to participate in the regulation of Akt1 kinase activity. (physiology.org)
Background: Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many cellular programs, such as cell proliferation, differentiation, motility, and death. (cellsignal.com)

The activation of protein kinase B (PKB, also known as c-Akt) is stimulated by insulin or growth factors and results from its phosphorylation at Thr308 and Ser473. (nih.gov)
The P70-S6K-dependent increase in rods appears to be correlated with phosphorylation of Thr252 and not at Thr389, a substrate of mTORC-1. (selleckchem.com)
Treatment with fMLF induced phosphorylation of soluble N -ethylmaleimide-sensitive factor-attachment protein (SNAP)-23, syntaxins 2, 4, and 6, and Monc18-3. (jimmunol.org)
However, LY294002 was less effective in inhibiting Munc18-3 phosphorylation. (jimmunol.org)
These results suggest that PKG and PI3K are involved in degranulation, possibly through phosphorylation of target membrane SNAP receptor proteins and their binding proteins. (jimmunol.org)
Research conducted thus far has led to the identification of several important regulatory mechanisms for leukocyte degranulation, including elevation of intracellular Ca 2+ concentration, activation of the cytoskeletal contractile apparatus, and phosphorylation of the soluble N -ethylmaleimide-sensitive factor-attachment protein (SNAP) 3 receptor proteins (SNAREs). (jimmunol.org)
Phosphorylation of Munc18-1 in neuronal cells ( 10 , 11 ) and Munc18-3 and syntaxin 4 in endothelial cells ( 12 ) promotes Munc18-syntaxin dissociation, thereby facilitating vesicular fusion. (jimmunol.org)
Phosphorylation of syntaxins, Munc18, and SNAP-23 is catalyzed by kinases such as protein kinase C (PKC) ( 12 , 13 , 14 ). (jimmunol.org)
In mast cells, a mechanism of degranulation induced by FcεRI cross-linking involves recruitment and activation of the tyrosine kinases Lyn and Syk, phosphorylation of several tyrosine residues in FcεRI, activation of phospholipase Cγ (PLCγ), and generation of the second messengers diacylglycerol and inositol trisphosphate ( 1 , 15 ). (jimmunol.org)
Protein phosphorylation transduces a large set of intracellular signals. (rcsb.org)
One mechanism by which phosphorylation mediates signal transduction is by prompting conformational changes in the target protein or interacting proteins. (rcsb.org)
Using a phospho-Akt substrate antibody, the phosphorylation of actin on an Akt consensus site was detected upon growth factor stimulation, both in cellulo and in vitro , suggesting that actin is a substrate of Akt kinase activity. (mcponline.org)
Class (I) PI3Ks (PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ) mediate the phosphorylation of the inositol ring at position D3 leading to the generation of PtdIns(3,4,5)P3. (mdpi.com)
We recently observed that phosphorylation of the AKT hydrophobic motif was dramatically elevated, rather than decreased, in mTOR knockout heart tissues, indicating the existence of other kinase(s) contributing to AKT phosphorylation. (pnas.org)
Accumulating evidence indicates an mTOR-independent kinase responsible for AKT (S473) phosphorylation. (pnas.org)
Akt is partially activated through PDK-1-mediated phosphorylation in the catalytic domain, but full activation requires a second phosphorylation event in the hydrophobic motif, which can be mediated by several kinases. (aacrjournals.org)
Negative feedback regulation of Akt can occur through S6K1, which can catalyze an inhibitory phosphorylation on insulin receptor substrate proteins, abrogating activation of PI3K. (aacrjournals.org)
Sphingosine 1-phosphate (S1P) is a bioactive lipid mediator, formed by the phosphorylation of sphingosine by sphingosine kinases (SphKs) 1 and 2, which participates in the regulation of a variety of biological activities in different cell types ( Pitson, 2011 ). (frontiersin.org)
The acute phosphorylation of phosphatidylinositol lipids at the D-3 position of the inositol ring in response to cell stimulation by growth factors and hormones sets in motion a coordinated set of events leading to cell growth, cell cycle entry, cell migration, and cell survival. (sciencemag.org)
These proteins are located in the cytosol of unstimulated cells but, in response to lipid phosphorylation, accumulate at the plasma membrane because of their ability to associate with the newly formed phosphoinositides. (sciencemag.org)
This phosphorylation stimulates the catalytic activity of Akt, resulting in the phosphorylation of a host of other proteins that affect cell growth, cell cycle entry, and cell survival. (sciencemag.org)
Most of the known protein targets of Akt become inhibited by the phosphorylation event. (sciencemag.org)
For example, phosphorylation of the Forkhead-related transcription factor 1 (FKHR-L1) by Akt creates a binding site for the 14-3-3 family of proteins ( 4 ). (sciencemag.org)
Similarly, Akt phosphorylation of the apoptosis-inducing protein Bad creates a binding site for 14-3-3 proteins and prevents Bad from binding to Bcl-2 family members Bcl-2 and Bcl-X L , thus releasing them for a cell survival response ( 4 ). (sciencemag.org)
Insulin binding to its receptor results in the tyrosine phosphorylation of insulin receptor substrates (IRS) by the insulin receptor tyrosine kinase (INSR). (genome.jp)
may catalyze the phosphorylation and activation of protein kinase B [RGD, Feb 2006]. (origene.com)
BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). (sciencemag.org)
Phosphorylation of BAD results in its cytosolic sequestration by the tau form of 14-3-3 proteins and its inactivation, as the phosphorylated form has reduced ability to bind to membrane Bcl-x L ( 3 ). (sciencemag.org)
Stimulation of the cells with IL-3 resulted in BAD phosphorylation that was inhibited by concentrations of wortmannin and LY294002 known to specifically inhibit PI 3-kinase activity (Fig. 1 ). (sciencemag.org)
PI 3-kinase inhibitors block IL-3-induced BAD phosphorylation in FL5.12 cells. (sciencemag.org)
Insulin's metabolic effects are mediated by a broad array of tissue-specific actions that involve rapid changes in protein phosphorylation and function, as well as changes in gene expression. (jci.org)
The initial molecular signal for insulin action involves activation of the insulin receptor tyrosine kinase, which results in phosphorylation of insulin receptor substrates (IRSs) on multiple tyrosine residues. (jci.org)
Membrane-associated Akt is activated by Ser 473 phosphorylation by membrane-associated phosphoinositide-dependent kinase-1 ( 3 ) and Thr 308 phosphorylation by a second incompletely characterized phosphoinositide-dependent kinase-2 ( 4 ). (aacrjournals.org)
The full activation of Akt1 kinase requires phosphorylation of both Thr-308 and Ser-473 ( 1 ). (physiology.org)
During ER stress, the stress signal induces ER transmembrane protein PRKR-like endoplasmic reticulum kinase (PERK) phosphorylation. (aacrjournals.org)
Here, we merge essential aspects of all three malaria-related communications that were presented at the Evolution of Protein Phosphorylation meeting, and propose an integrated discussion of the specific features of the parasite's kinome and phosphoproteome. (royalsocietypublishing.org)
Small molecule substrate phosphorylation site inhibitors of protein kinases: approaches and challenges. (ebi.ac.uk)

GRB2 is part of the cascade including SOS, RAS, RAF and MEK that leads to activation of mitogen-activated protein kinase (MAPK) and mitogenic responses in the form of gene transcription. (genome.jp)
Remarkably, nearly all KRAS deficient cells exhibit phosphoinositide 3-kinase (PI3K)-dependent mitogen-activated protein kinase (MAPK) signaling and induced sensitivity to PI3K inhibitors. (nature.com)
Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by 2-Hydroxy Branched-Chain Amino Acid Second Messengers during Osmotic Stress. (unc.edu)
mitogen-activated protein kinase 4 [EC:2.7.1. (wikipathways.org)
We show that Gab1 associates with the EGFR in vivo and in vitro via pTyr sites 1068 and 1086 in the carboxy-terminal tail of the receptor and that overexpression of Gab1 potentiates EGF-induced activation of the mitogen-activated protein kinase and Jun kinase signaling pathways. (asm.org)
These phosphorylations recruit signal transducers leading to activation of signaling pathways that include the Ras/mitogen-activated protein kinase kinase/mitogen-activated protein kinase pathway, the signal transducers and activators of transcription pathway, and the PI3-K/Akt survival pathway. (aacrjournals.org)

In rat basophilic leukemia-2H3 cells expressing formyl peptide receptor, the PKG inhibitors KT5823 and Rp-8-Br-PET-cGMP, as well as the PI3K inhibitor LY294002, reduced agonist-stimulated β-hexosaminidase release in a dose-dependent manner. (jimmunol.org)
Kinetics of PDK-1 inhibition by celecoxib with respect to ATP suggest that celecoxib derivatives inhibit PDK-1 by competing with ATP for binding, a mechanism reminiscent to that of many kinase inhibitors. (aacrjournals.org)
A screen of 72 inhibitors against 456 human kinases. (guidetoimmunopharmacology.org)
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfiler TM service. (guidetoimmunopharmacology.org)
A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase Hotspot SM platform. (guidetoimmunopharmacology.org)
The response to GLP-1 was mimicked by forskolin and largely inhibited by the protein kinase A (PKA) inhibitors, H89 and myristoylated PKI(14-22) amide, indicating partial mediation via a cAMP/PKA pathway. (diabetesjournals.org)
Following the regulatory approval of the rapamycin analogs everolimus and temsirolimus, recent years have seen an explosion in the number of phosphoinositide 3-kinase (PI3K) pathway inhibitors under clinical investigation. (aacrjournals.org)
Targeting key tyrosine kinases (TKs) with TK antibodies and inhibitors has a remarkable achievement in cancer management. (frontiersin.org)
In perfused rat liver, PI3-kinase inhibitors largely abolished the stimulatory effect of TUDC on taurocholate excretion, suggesting an important role for a PI3-kinase/Ras/Erk pathway in the choleretic effect of TUDC. (portlandpress.com)
In particular, we describe recent preclinical and clinical trials of therapies targeting S1P signaling, including 2-amino-2-propane-1,3-diol hydrochloride (FTY720, fingolimod), S1P receptor agonists, sphingosine kinase inhibitors, and anti-S1P monoclonal antibody. (aspetjournals.org)
FL5.12 cells were stimulated with recombinant IL-3 in the presence or absence of PI 3-kinase inhibitors, and the kinase activity of endogenous Akt was assayed in Akt immunoprecipitates with the use of histone H2B as a substrate ( 6 ). (sciencemag.org)
The G0/G1 phase arrest correlated with increase levels of CDK inhibitors (p16, p21 and p27) and decrease of the checkpoint proteins. (nature.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)
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)
Structural analysis of the lymphocyte-specific kinase Lck in complex with non-selective and Src family selective kinase inhibitors. (ebi.ac.uk)
The structures of these Lck complexes offer useful structural insights as they demonstrate that kinase selectivity can be achieved with small-molecule inhibitors that exploit subtle topological differences among protein kinases. (ebi.ac.uk)
Interleukin-1 receptor associated kinase inhibitors: potential therapeutic agents for inflammatory- and immune-related disorders. (ebi.ac.uk)
Update on lymphocyte specific kinase inhibitors: a patent survey. (ebi.ac.uk)
Tyrphostins and other tyrosine kinase inhibitors. (ebi.ac.uk)
Structural biology in drug design: selective protein kinase inhibitors. (ebi.ac.uk)
Our findings imply that signal transduction inhibitors that lead to a modest reduction in Akt activity would not only delay onset of tumours possessing elevated phosphoinositide 3-kinase pathway activity but would also reduce the growth rate of developed tumours. (biologists.org)

Protein kinase B (PKB), also known as c-Akt, is activated rapidly when mammalian cells are stimulated with insulin and growth factors, and much of the current interest in this enzyme stems from the observation that it lies 'downstream' of phosphoinositide 3-kinase on intracellular signalling pathways. (nih.gov)
These conditions are ideal to trigger the inflammatory pathways leading to activation of I κ B kinase (IKK) and related kinases, which affect insulin signaling at its bottleneck by phosphorylating and switching off the function of insulin receptor substrate (IRS). (hindawi.com)
On the one hand, ROS triggers the activation of different cellular pathways by activating specific proteins (e.g. (intechopen.com)
These data suggest that the synergistic action of glucose and GLP-1 to promote insulin gene transcription is mediated through NFAT via PKA- and calcineurin-dependent pathways in pancreatic β-cells. (diabetesjournals.org)
AMPK phosphorylates and regulates many proteins concerned with nutrient metabolism, largely acting to suppress anabolic ATP-consuming pathways while stimulating catabolic ATP-generating pathways. (clinsci.org)
The noncanonical IκB kinase ε (IKKε) has been demonstrated to play an essential role in Ras-induced cell transformation, which requires activation of both the Raf-MEK-ERK and PI3K-AKT pathways ( 20 ). (pnas.org)
In this review we summarize metabolism of S1P, mechanisms of sphingosine kinase activation, and S1P receptors and their downstream signaling pathways and examine relationships to multiple disease processes. (aspetjournals.org)
Pharmacological screening of signalling pathways activated under the high-affinity NT-4 receptor TrkB (tropomyosin receptor kinase B) identified a role for PI3K (phosphoinositide 3-kinase) in the potentiation of T-current. (biochemj.org)
In the case of receptor tyrosine kinases (RTKs), these processes include cell growth, survival, differentiation, and transformation, all of which depend on the activation of multiple signaling pathways ( 45 ). (asm.org)
PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. (origene.com)
In particular, specific proteins and molecular pathways, affecting cell cycle progression and apoptosis, have been extensively studied and shown to be targeted by celecoxib ( 12 - 17 ). (aacrjournals.org)
It is becoming evident that specific members of the AGC kinases are implicated in key growth signalling pathways. (mendeley.com)
They are primarily characterized through the accumulation of modified proteins, which further trigger biological responses such as inflammation, oxidative stress, excitotoxicity and modulation of signalling pathways. (biomedcentral.com)

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)
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)
PDPK1 stands for 3-phosphoinositide-dependent protein kinase 1. (wikipedia.org)
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)
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)
Several PDPK1 substrates including S6K and Protein kinase C, require the binding at this docking site. (wikipedia.org)
PDPK1 is constitutively active and at present, there is no known inhibitor proteins for PDPK1. (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)
This affinity purified antibody was prepared from whole rabbit serum produced by repeated immunizations with a synthetic peptide corresponding to a region near the C-terminal of human PDPK1 protein. (novusbio.com)
Homo sapiens 3-phosphoinositide dependent protein kinase-1 (PDPK1), mRNA. (abnova.com)

Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha. (nih.gov)
Glucose metabolism activates this pathway by means of increasing [Ca 2+ ] i via L-type voltage-dependent calcium channels (VDCCs) by affecting the electrical activity of the cell. (diabetesjournals.org)
Mechanistically, it is known that GLP-1 increases cyclic AMP in pancreatic β-cells by its action on the Gs-coupled GLP-1 receptor, which in turn, activates cAMP-dependent protein kinase A (PKA) ( 21 ). (diabetesjournals.org)
Upon activation by receptor tyrosine kinase PI3K phosphorylates PIP2 to PIP3 which then activates Akt signaling. (antibodies-online.com)

In our previous studies we showed antitumor and anti-inflammatory activities of protein kinases inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF3-fenylamino)-1H-pyrrol-2,5-dione (MI-1) on rat colon cancer model. (hindawi.com)
Protein kinase inhibitor pyrrol derivate 1-(4-Cl-benzyl)-3-Cl-4-(CF 3 -fenylamino)-1Н-pyrrol-2,5-dione (MI-1) (Figure 1 ) has been synthesized at Chemistry Department of Taras Shevchenko National University of Kyiv. (hindawi.com)
Significantly, the actions of both GLP-1 and forskolin were abolished by the selective Ca 2+ /calmodulin-dependent phosphatase 2B (calcineurin) inhibitor, FK506, as well as by the chelation of intracellular Ca 2+ by BAPTA (bis(2-aminophenoxy)ethane- N,N,N ′ ,N ′-tetraacetate). (diabetesjournals.org)
Mass spectrometry analysis (MALDI-TOF and MS-MS) of SDS-PAGE-separated Akt co-immunoprecipitates allowed the identification of 10 proteins: α -actinin, valosin-containing protein, inhibitor κB kinase, mortalin, tubulin β, cytokeratin 8, actin, 14-3-3σ, proliferating cell nuclear antigen, and heat shock protein HSP27. (mcponline.org)
The PI3-kinase activity of this protein is not sensitive to nanomolar levels of the inhibitor wortmanin. (origene.com)
however, one of mTOR effectors, ribosomal protein S6 kinase 1 (S6K1), is a feedback inhibitor of insulin- and insulin-like growth factor (IGF)-induced PI3K activation. (aacrjournals.org)
A selective COX-2 inhibitor, celecoxib, has shown efficacy in reducing polyp burden in patients with the inherited syndrome familial adenomatous polyposis and, more recently, with sporadic adenomas ( 2 , 3 , 5 ). (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)
and PP2 (a potent Src family selective protein tyrosine kinase inhibitor). (ebi.ac.uk)

Serum Cyr61 levels were correlated with disease characteristics and the association between Cyr61 expression changes by several types of stimulation or stress and cAMP/cAMP-dependent protein kinase (PKA) pathway were examined. (pubmedcentralcanada.ca)
Several proteins such as heat shock protein 27, 70, and 90, CDC2, α-tubulin, annexin A3, cAMP-dependent protein kinase, glycogen synthase kinase 3-beta, and β-catenin were identified by proteomics and confirmed by Western blot. (aacrjournals.org)
In addition, molecular modeling showed that OSU03013 competes with ATP to bind to cAMP-dependent protein kinase. (aacrjournals.org)
We identified for the first time that OSU03013 inhibits cAMP-dependent protein kinase activity and causes dephosphorylation of glycogen synthase kinase 3-beta leading to β-catenin degradation, which is often overexpressed in lung cancer. (aacrjournals.org)

The blockade of Akt activation through the inhibition of 3-phosphoinositide-dependent kinase-1 (PDK-1) represents a major signaling mechanism whereby celecoxib mediates apoptosis. (aacrjournals.org)
Structure-activity analysis together with molecular modeling was used to generate compounds that were tested for their potency in inhibiting PDK-1 kinase activity and in inducing apoptosis in PC-3 prostate cancer cells. (aacrjournals.org)
The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway controls many cellular processes that are important for the formation and progression of cancer, including apoptosis, transcription, translation, metabolism, angiogenesis, and cell cycle progression. (aacrjournals.org)
Heterozygous disruption of Pik3r1 results in increased Akt activity and decreased apoptosis by insulin-like growth factor 1 (IGF-1) through up-regulated phosphatidylinositol (3,4,5)-triphosphate production. (asm.org)
Complete depletion of p85α, on the other hand, results in significantly increased apoptosis due to reduced PI 3-kinase-dependent signaling. (asm.org)
Expression levels of cell cycle regulatory proteins and apoptosis-related proteins were determined after Tan-IIA treatment. (nature.com)
16 also reported that Tan-IIA induced mitochondria-dependent apoptosis by inhibiting the phosphoinositide 3-kinase/protein kinase B pathway in LNCaP prostate cancer cells. (nature.com)

A third target of Akt is glycogen synthase kinase 3 (GSK3). (sciencemag.org)
Akt in turn deactivates glycogen synthase kinase 3 (GSK-3), leading to activation of glycogen synthase (GYS) and thus glycogen synthesis. (genome.jp)

Upon stimulation, a sequential three-part protein kinase cascade is initiated, consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). (cellsignal.com)

Interestingly it has been suggested that activation of Akt1 by Her2/phosphatidylinositol 3-kinase (PI3K) plays an important role in mediating multidrug resistance in human breast cancer cells, and Akt may therefore be a novel molecular target for therapies against breast cancer (2, 4). (mcponline.org)
Basal and insulin-stimulated activity of Akt1 kinase and uptake of 2-deoxy- d -glucose (2-DG) were measured in soleus (slow-twitch) and plantaris (fast-twitch) muscles of rats at 1 and 3 days after sectioning the sciatic nerve in one hindlimb of the animals. (physiology.org)
At 1 day after surgery, the insulin-stimulated activity of Akt1 kinase in denervated soleus and plantaris muscles remained unchanged, but the insulin-stimulated 2-DG uptake by these muscles was reduced by 71 and 61%, respectively, compared with the corresponding muscles of the contralateral sham (control) hindlimb. (physiology.org)
At 3 days, the insulin-stimulated activity of Akt1 kinase in the denervated soleus and plantaris muscles was 86 and 71% lower, respectively, than in their sham counterparts. (physiology.org)
None of the denervated muscles showed a decrease in the abundance of Akt1 kinase. (physiology.org)
Initially, they involve only mechanisms downstream of Akt1 kinase ( day 1 ), whereas at day 3 they also involve mechanisms upstream of, and including, Akt1 kinase. (physiology.org)
The product of the phosphatidylinositol 3-kinase reaction, phosphatidylinositol 3,4,5-trisphosphate, may serve as a link to the activation of 3-phosphoinositide-dependent protein kinase-1 ( 9 ), which in turn phosphorylates Akt1 kinase, also referred to as protein kinase B or RAC kinase, at Thr-308 ( 2 ). (physiology.org)
The role of Akt1 kinase in mediating the insulin-induced stimulation of glucose uptake is suggested by the observation that transfection of a constitutively active Akt1 kinase into 3T3-L1 adipocytes has an insulin-like effect on the translocation of GLUT-4 transporter to the plasma membrane and glucose uptake ( 13 ). (physiology.org)
The regulation of Akt1 kinase activity is incompletely understood. (physiology.org)

Inhibition of PDPK-1-dependent kinases, such as P70-S6K, but not others, such as mTORC-1, stimulated rod development. (selleckchem.com)
We also found that inhibition of the kinase mTORC-2, also stimulated by insulin activity, similarly increased rod formation, and this effect appears to be independent of PKC activity. (selleckchem.com)
Exposure of PC-3 cells to these agents led to Akt dephosphorylation and inhibition of p70 S6 kinase activity. (aacrjournals.org)
Screening in a panel of 60 cell lines and more extensive testing in PC-3 cells indicated that the mean concentration for total growth inhibition was ∼3 μ m for both agents. (aacrjournals.org)
Inhibition of the NF-kappaB, p53, or Rb pathway proved insufficient to prevent kinase-triggered cell cycle arrest. (senescence.info)
Inhibition of PI-3 kinase by a dominant-interfering mutant of p85 or by Wortmannin treatment similarly impairs Gab1-induced enhancement of signaling via the EGFR. (asm.org)
In POMC neurons the insulin receptor (InsR) couples to phosphatidylinositol 3-kinase (PI3K) p110β activation (14, 15), and the InsR-mediated excitation of POMC neurons is abrogated by inhibition of PI3K activity (9, 15-17). (deepdyve.com)

PDPK-1 is a 63 kDa cytoplasmic kinase that controls cell proliferation and differentiation. (selleckchem.com)
Phosphoinositide 3-kinases (PI3Ks) are a diverse family of enzymes which regulate various critical biological processes, such as cell proliferation and survival. (mdpi.com)

The regulatory and catalytic properties of the three mammalian isoforms of protein kinase B (PKB) have been compared. (biochemj.org)
SIRT1 (silent information regulator 1), a member of mammalian sirtuin family protein (SIRT1-SIRT7), functions as a conserved nicotinamide adenine dinucleotide (NAD)+-dependent deacetylase to implicate in the modulation of transcriptional silencing and cell survival. (springer.com)
Signaling through the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway can be initiated by several mechanisms that lead to the generation of 3′-phosphoinositides by PI3K ( Fig. 1 ). (aacrjournals.org)
Proteins of the Bcl-2 family are important regulators of cell death in mammalian cells ( 1 ). (sciencemag.org)

Incubate membrane with Anti-rabbit IgG, HRP-linked Antibody ( #7074 at 1:2000) and anti-biotin, HRP-linked Antibody ( #7075 at 1:1000-1:3000) to detect biotinylated protein markers in 10 ml of blocking buffer with gentle agitation for 1 hr at room temperature. (cellsignal.com)

PI3K signaling is initiated by receptor tyrosine kinases (RTK) or G-protein-coupled receptors located at the cell surface, and some oncogenic proteins, such as RAS. (aacrjournals.org)
The lymphocyte-specific kinase Lck is a member of the Src family of non-receptor tyrosine kinases. (ebi.ac.uk)

Since G protein coupled receptors (GPCRs) are target of forty percent of clinically used drugs, here we discuss the newly identified cardioprotective agents that bind GPCRs of adrenalin, adenosine, melatonin, ghrelin, galanin, apelin, prokineticin and cannabidiol. (frontiersin.org)
S1P is synthesized by sphingosine kinases (SphKs) and many of its actions are mediated by S1P specific cell surface receptors (S1P 1-5 ), although different intracellular targets of S1P have been identified. (frontiersin.org)
Activation of sphingosine kinase by a variety of agonists increases intracellular S1P, which in turn can function intracellularly as a second messenger or be secreted out of the cell and act extracellularly by binding to and signaling through S1P receptors in autocrine and/or paracrine manners. (aspetjournals.org)
Gene deletion studies and reverse pharmacology have provided evidence that many of the biological effects of S1P are mediated via five specific G protein-coupled receptors (GPCRs), now designated S1P 1-5 ( Fig. 3 ). (aspetjournals.org)
The regulatory subunit maintains the p110 catalytic subunit in a low-activity state in quiescent cells and mediates its activation by direct interaction with phosphotyrosine residues of activated growth factor receptors or adaptor proteins. (sciencemag.org)
These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. (antibodies-online.com)
This gene product belongs to a family of glutamate receptors that are sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and function as ligand-activated cation channels. (antibodies-online.com)
PI 3-kinase is recruited and activated during the intracellular signal transduction of many receptors and has been implicated in the signaling of survival factors ( 5 ). (sciencemag.org)
However, a number of receptors also rely on a growing family of accessory, or docking, proteins that are recruited to the plasma membrane, become tyrosine phosphorylated, and act as centers for assembly of multiprotein complexes. (asm.org)
The National Cancer Institute, Division of Cancer Prevention has recently ublished a series of reviews on mechanism-based targets for cancer-preventive intervention including peroxisome proliferator-activated receptors ( 1 ), inducible nitric oxide synthase ( 2 ), and epigenetic modulators, primarily histone deacetylases and DNA methyl transferases ( 3 , 4 ). (aacrjournals.org)

SNAREs, which were initially identified in neuronal cells for their function in membrane fusion ( 5 ), include vesicular SNAREs such as vesicle-associated membrane proteins, target membrane SNAREs (t-SNAREs) such as syntaxins, and the Sec1/Munc18 family of proteins that serve as binding partners of t-SNAREs. (jimmunol.org)
Membrane fusion proteins cooperate to promote rapid secretory vesicle exocytosis from neuroendocrine cells. (sciencemag.org)
The PIK3CG:PIK3R6 heterodimer is much less sensitive to beta-gamma G proteins than PIK3CG:PIK3R5 and its membrane recruitment and beta-gamma G protein dimer-dependent activation requires HRAS bound to PIK3CG. (uniprot.org)
Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. (uniprot.org)
Once generated, 3′-phosphoinositides bind to the pleckstrin homology domains of 3′-phosphoinositide-dependent kinase-1 (PDK-1) and Akt and cause translocation of each kinase to the plasma membrane, where both are activated. (aacrjournals.org)
At the membrane, these proteins become activated and initiate various local responses, including polymerization of actin, assembly of signaling complexes, and priming of protein kinase cascades. (sciencemag.org)
The activated PI3K converts the plasma membrane lipid phosphatidylinositol-4,5-bisphosphate [PI(4,5)P 2 ] to phosphatidylinositol-3,4,5-trisphosphate [PI(3,4,5)P 3 ]. (sciencemag.org)
This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. (antibodies-online.com)
Finally, expression of the gene for the lipid phosphatase PTEN, which dephosphorylates PtdIns(3,4,5)P3, inhibits EGF signaling and translocation of Gab1 to the plasma membrane. (asm.org)

Overall, brain health and successful aging are characterized by limited protein aggregation, with a distinct molecular signature of maintained autophagy function. (intechopen.com)
Optimal signaling through the PI 3-kinase pathway depends on a critical molecular balance between the regulatory and catalytic subunits. (asm.org)
a ) Chemical structure of Tan-IIA, C 19 H 18 O 3 , molecular weight: 294.34. (nature.com)
Binding of calcium to the protein calmodulin leads to molecular reorganization that enables interaction with target peptides and activation of downstream processes. (dissertations.se)
The scope of celecoxib-modulated molecular alterations can best be studied by applying global approaches at the transcription and/or protein levels. (aacrjournals.org)
We examined the interaction between OSU03013 and potential target protein by molecular modeling. (aacrjournals.org)
Loading of prestained molecular weight markers ( #13953 , 5 µl/lane) to verify electrotransfer and biotinylated protein ladder ( #7727 , 10 µl/lane) to determine molecular weights are recommended. (cellsignal.com)

The effect of Ptdlns(3,4,5)P3/Ptdlns(3,4)P2 in the activation of PKB alpha is at least partly substrate directed. (nih.gov)
Following IGF-1 and insulin stimulation, the tyrosine-phosphorylated pYMXM and pYXXM motifs in the insulin receptor substrate (IRS) proteins bind to class Ia PI 3-kinase, thereby increasing its activity ( 2 , 43 ). (asm.org)
S6K1, stimulated by activated mTOR, phosphorylates insulin receptor substrate proteins, inhibiting their function, which in turn diminishes signaling through the PI3K/AKT pathway (reviewed in refs. (aacrjournals.org)

This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. (origene.com)

Online Cover This week features a Research Article that identifies ARAP3 as the downstream effector of phosphoinositide 3-kinase (PI3K) in the regulation of sprouting angiogenesis during development. (sciencemag.org)
The AKT protein kinase is a major signaling hub and a key downstream effector of the PI3K pathway ( 1 , 2 ). (pnas.org)
For example, PDK-1 can regulate translation independently of Akt by directly phosphorylating and activating a downstream effector of mTOR, S6 kinase-1 (S6K1). (aacrjournals.org)
A mutant of Gab1 unable to bind the p85 subunit of PI-3 kinase is defective in potentiating EGFR signaling, confirming a role for PI-3 kinase as a downstream effector of Gab1. (asm.org)
These results reveal a novel positive feedback loop, modulated by PTEN, in which PI-3 kinase functions as both an upstream regulator and a downstream effector of Gab1 in signaling via the EGFR. (asm.org)
The uncoupling of the insulin receptor from its downstream effector system was corroborated by the reduced expression of phosphorylated protein kinase B in the arcuate nucleus of male but not female guinea pigs following insulin. (deepdyve.com)

We have previously identified NFAT (nuclear factor of activated T-cells) as a key regulator of insulin gene transcription in pancreatic β-cells that is activated by the calcium/calmodulin-dependent protein phosphatase 2B (calcineurin) in response to increased [Ca 2+ ] i ( 10 ). (diabetesjournals.org)
Class Ia phosphoinositide (PI) 3-kinase is a central component in growth factor signaling and is comprised of a p110 catalytic subunit and a regulatory subunit, the most common family of which is derived from the p85α gene ( Pik3r1 ). (asm.org)
This gene is a target gene of the transcription factor tumor protein p53. (antibodies-online.com)
Overexpression of this gene can result in excessive inactivation of tumor protein p53, diminishing its tumor suppressor function. (antibodies-online.com)
The protein encoded by this gene belongs to the highly conserved cyclin family, whose members are characterized by a dramatic periodicity in protein abundance through the cell cycle. (antibodies-online.com)
6 ⇓ - 8 In 1994, 2 independent groups cloned the genes involved in this translocation and illustrated the fusion of the nucleophosmin ( NPM ) gene on chromosome 5q35 to the previously unidentified gene anaplastic lymphoma kinase ( ALK ) gene on 2p23. (bloodjournal.org)
More recently, targeted disruption of the IRS-2 gene was shown to result in a generation of diabetic mice, demonstrating a role for this docking protein in signaling by the insulin receptor ( 54 ). (asm.org)
The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. (origene.com)
The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. (senescence.info)

Belongs to the protein kinase superfamily. (abcam.com)
This transmembrane receptor tyrosine kinase belongs to the insulin receptor superfamily. (bloodjournal.org)

Other signal transduction proteins interact with IRS including GRB2. (genome.jp)
Phosphoinositides (PIs) play major roles in cell signal transduction. (dissertations.se)

Activation of intracellular NLR by a variety of microbial molecules leads to PF-5274857 inflammasome formation caspase-1 activation and subsequent formation and release of interleukin-1β (IL-1β) thereby creating an intracellular surveillance system for pathogens [2] [3]. (exposed-skin-care.net)
Intracellular calcium ([Ca 2+ ] i ) appears to be an important mediator of this process ( 3 , 6 - 10 ). (diabetesjournals.org)
Autophagy is the major intracellular system which is critical for the removal of harmful protein aggregates and malfunctioning organelles. (intechopen.com)

This chromosomal translocation induces the formation of the chimeric protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), which possesses significant oncogenic potential resulting from the constitutive activation of the tyrosine kinase ALK. (bloodjournal.org)

The 556-residue monomeric enzyme comprises a catalytic domain that is most similar to the PKA, PKB and PKC subfamily of protein kinases and a carboxy-terminal pleckstrin homology (PH) domain. (nih.gov)
Signaling proteins with pleckstrin-homology (PH) domains accumulate at sites of PI3K activation by directly binding to PI(3,4,5)P 3 . (sciencemag.org)

Akt protein modulates the function of several downstream substrates involved in the regulation of cell survival, cell cycle progression, and cellular growth. (mcponline.org)
The receptor tyrosine kinase phosphorylates insulin receptor substrates (IRS), which enables the regulatory subunit (p85) of phosphatidylinositol 3-kinase to bind to IRS. (physiology.org)
During this time I mainly gained interests on how glycosyltransferases modifying proteins achieve recognition and catalysis on protein substrates. (google.com)

The role of Epac proteins, novel cAMP mediators, in the regulation of immune, lung and neuronal function. (semanticscholar.org)
The pathway maps illustrate protein interactions and regulation to provide a comprehensive picture of signaling and disease processes. (bio-rad.com)
Three mechanisms of K+-Cl− COT regulation can be identified in vascular cells: (1) the Li+-sensitive pathway, (2) the platelet-derived growth factor (PDGF)-sensitive pathway and (3) the nitric oxide (NO)-dependent pathway. (ovid.com)
Regulation by PDGF involves the signalling molecules phosphoinositides 3-kinase and protein phosphatase-1. (ovid.com)

BX-912 is a small molecule that inhibits 3-phosphoinositide dependent protein kinase-1. (wikipedia.org)
The encoded protein is a nuclear phosphoprotein that binds and inhibits transactivation by tumor protein p53, as part of an autoregulatory negative feedback loop. (antibodies-online.com)

The class Ia PI 3-kinases are dimers composed of a p110 catalytic subunit and a regulatory subunit with SH2 domains which can interact with IRS proteins ( 17 , 52 ). (asm.org)
This allows association of IRSs with the regulatory subunit of phosphoinositide 3-kinase (PI3K). (genome.jp)
These phosphotyrosine residues act as docking sites for many SH2 domain-containing proteins, including the p85 regulatory subunit of phosphoinositide 3′ kinase (PI3K). (jci.org)

PtdIns(3,4,5)P3 can be dephosphorylated by several phosphatases, of which the best known is the 3-phosphatase PTEN (phosphatase and tensin homolog). (mdpi.com)
The tumor suppressor phosphatase and tensin homologue deleted on chromosome 10 (PTEN) opposes the action of PI3K by dephosphorylating 3′-phosphoinositides. (aacrjournals.org)
suggesting that the effects of Pten deletion on neurodevelopment are mediated primarily through PI3K-derived mTOR activation and protein synthesis. (biologists.org)
The tumor suppressor protein PTEN (phosphatase and tensin homologue deleted on chromosome 10), a dual specificity tyrosine-threonine/PI-3 phosphatase, prevents the accumulation of PI(3,4,5)P 3 and attenuates PI3-K signaling ( 9 ). (aacrjournals.org)

This is achieved in tissue-specific manner via increased translocation of the insulin-dependent glucose carrier GLUT4 in the skeletal muscle and fat cells [ 2 , 3 ] and increased expression of GLUT1 in vascular endothelium cells [ 4 ]. (hindawi.com)
The translocation of GLUT4 protein is also elicited through the CAP/Cbl/TC10 pathway, once Cbl is phosphorylated by INSR. (genome.jp)
9 , 10 This chromosomal translocation leads to the generation of the chimeric protein NPM-ALK. (bloodjournal.org)
Identifying these tumors with this translocation became clinically feasible after the production of antibodies that specifically interact with chimeric NPM-ALK and full-length ALK proteins. (bloodjournal.org)
Tan-IIA also induced ER stress in prostate cancer cells: activation and nuclear translocation of GADD153/CCAAT/enhancer-binding protein-homologous protein (CHOP) were identified, and increased expression of the downstream molecules GRP78/BiP, inositol-requiring protein-1α and GADD153/CHOP were evidenced. (nature.com)
C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. (origene.com)

Direct binding of p110 to activated Ras protein (also induced by growth factor stimulation) further stimulates PI3K activity. (sciencemag.org)
The binding of p85 to IRS then results in the activation of the catalytic subunit (p110) of phosphatidylinositol 3-kinase ( 7 ). (physiology.org)

Liver fibrosis is an excess production of extracellular matrix proteins as a result of chronic liver disease which leads to cell death and organ dysfunction. (frontiersin.org)
Ras activation by TUDC was followed by an activation of the mitogen-activated protein kinases extracellular-signal-regulated kinase-1 (Erk-1) and Erk-2. (portlandpress.com)
Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling. (pubmedcentralcanada.ca)
Cystein-rich angiogenic inducer 61 (Cyr61), also called CCN1, is an extracellular matrix protein involved in growth factor transduction, hormone signaling, and mechanical stress response mediation [ 3 ]. (pubmedcentralcanada.ca)
They include the epidermal growth factor receptor (EGFR, ErbB-1, HER1), that when activated by ligand binding to its extracellular domain, homodimerizes or heterodimerizes with any of three other family members, ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4), leading to autophosphorylation of cytoplasmic COOH-terminal tyrosine residues. (aacrjournals.org)

The PH domain of Gab1 was shown to bind specifically to phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3], a product of PI-3 kinase, and is required for activation of Gab1-mediated enhancement of EGFR signaling. (asm.org)

The pathway from insulin receptor type protein-tyrosine kinase to PI3K to Akt and FKHR-L1 is conserved from Caenhorhabditis elegans to mammals ( 5 ). (sciencemag.org)

We have purified 500 000-fold from rabbit skeletal muscle extracts a protein kinase which phosphorylates PKBalpha at Thr308 and increases its activity over 30-fold. (nih.gov)
Consistent with previous studies, stimulation of STAT3 activity is sufficient to prevent any PDPK-1, P70-S6K, or mTORC2-dependent increase in rods. (selleckchem.com)
Prednisolone decreased GTI to 3 and leveled SOD activity, but MDA and PCG remained higher than control ones by 52% and 42%, respectively. (hindawi.com)
Disrupting activity of the guanosine triphosphatase-activating protein ARAP3 is a potential strategy for anti-angiogenic therapy. (sciencemag.org)
Downstream of TLR4, SHP-1 showed increased interaction with several proteins including IL-1R-associated kinase-4, and modulated LPS signaling by inhibiting NF-κB, AP-1, ERK, and JNK activity, while enhancing p38 activity. (jimmunol.org)
Major interest exists in the dietary manipulation of the autophagy pathway activity, so as to tune the cell's protein degradation capabilities and to prevent cell death onset. (intechopen.com)
It has recently become clear that the machinery required to degrade protein cargo has a distinct activity level which can be altered through specific dietary modulation. (intechopen.com)
Ras activation was dependent on PI3-kinase activity, without the involvement of protein kinase C- and genistein-sensitive tyrosine kinases. (portlandpress.com)
Because Akt is a target of the PI 3-kinase, we determined next whether stimulation of FL5.12 cells with IL-3 could increase the activity of Akt through a PI 3-kinase-dependent mechanism. (sciencemag.org)
Stimulation with IL-3 increased Akt kinase activity four times and was inhibited by wortmannin and LY294002 (Fig. 2 ). (sciencemag.org)
The specific function of Cyr61 remains largely unknown but its biological activity is believed to be contextual and cell-type dependent [ 7 , 8 ]. (pubmedcentralcanada.ca)
mTOR regulates both transcription of genes relevant to carcinogenesis, including, for example, hypoxia inducible factor (HIF)-1α ( 14 - 17 ), and activity of the procarcinogenic phosphotidylinositol 3-kinase (PI3K)/AKT pathway ( 18 , 19 ). (aacrjournals.org)

Here we show that the atypical IκB kinase ε and TANK-binding kinase 1 (IKKε/TBK1) phosphorylate AKT on both the hydrophobic motif and the activation loop in a manner dependent on PI3K signaling. (pnas.org)
Collectively, these data provide compelling evidence for the existence of other AKT hydrophobic motif kinases besides mTORC2. (pnas.org)

Human recombinant protein fragment corresponding to amino acids 230-560 of human PIK3C2A produced in E.coli. (thermofisher.com)

NALP3 (formerly known as cryopyrin) belongs to the family of NLR proteins. (exposed-skin-care.net)
[3] The most important member of the auxin family is indole-3-acetic acid (IAA), [7] which generates the majority of auxin effects in intact plants, and is the most potent native auxin. (wikipedia.org)
PI3Ks are an enzyme family that phosphorylate PtdIns (Phosphatidylinositol) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). (antibodies-online.com)
AGC Ser/Thr protein kinase family. (abcam.com)
BAD, a distant member of the Bcl-2 family, promotes cell death at least in part through heterodimerization with the survival proteins Bcl-2 and Bcl-x L ( 2 ). (sciencemag.org)
mTOR is the target of rapamycin, a macrolide antibiotic and immunosuppressant of the phosphoinositide kinase family. (aacrjournals.org)
the amino acid composition of this pocket is unique to Src family kinases. (ebi.ac.uk)

The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is one of the most frequently dysregulated signaling cascades in human malignancies and is implicated in a wide variety of different neoplasms ( 1 ). (aacrjournals.org)

Akt/PKB was initially identified by three independent groups based on its homology to protein kinases A and C and to the cellular homolog of the retroviral oncogene Akt (v-Akt). (mcponline.org)
The original discovery of Akt kinase as the cellular homolog of a viral oncogene already implied its pivotal role in cell growth and survival that, since then, has been verified in various cell systems, and Akt is increasingly regarded as a crucial player in cancer cell survival and growth (2). (mcponline.org)
TANK-binding kinase 1 (TBK1) is the closest IKKε homolog, and a systematic RNA interference screen has identified that TBK1 is required for Ras-induced oncogenesis. (pnas.org)

Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)

AKT plays a major role in cell growth, proliferation, and survival ( 3 ). (pnas.org)
Based on these studies, it was unclear whether the "KRAS-independent" phenotype was a consequence of the incomplete inhibitory effects of RNAi such that residual KRAS protein was sufficient to sustain cell survival and proliferation. (nature.com)
PIP 3 mediates the recruitment and activation of kinases, adaptor proteins and small GTPases to regulate neurodevelopmental responses ranging from cell survival to synaptic development. (biologists.org)

p>When browsing through different UniProt proteins, you can use the 'basket' to save them, so that you can back to find or analyse them later. (uniprot.org)

S1P levels inside cells are tightly regulated by the balance between its synthesis by sphingosine kinases and degradation. (aspetjournals.org)
an aliphatic 18-carbon amino alcohol with an unsaturated hydrocarbon chain), by sphingosine kinases ( Fig. 2 ). (aspetjournals.org)

Upon activation NALP3 assembles with the adaptor protein ASC to form a protein-complex termed the PF-5274857 NALP3 inflammasome [4]. (exposed-skin-care.net)

Although multiple forms of phosphoinositide 3-kinases (PI3Ks) exist in higher eukaryotes, the class Ia enzymes are primarily responsible for production of D-3 phosphoinositides in response to growth factors ( 1 ). (sciencemag.org)

Anatomy22

Organisms11

Chemicals and Drugs160

Analytical, Diagnostic and Therapeutic Techniques and Equipment14

Phenomena and Processes45

Information Science3

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

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

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)

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

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

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

Protein Kinases

Protein Kinase C

Cyclic AMP-Dependent Protein Kinases

Phosphorylation

Calcium-Calmodulin-Dependent Protein Kinases

Phosphatidylinositol 3-Kinases

Enzyme Activation

Protein Kinase Inhibitors

Signal Transduction

Protein-Serine-Threonine Kinases

Calcium-Calmodulin-Dependent Protein Kinase Type 2

Calcium-Calmodulin-Dependent Protein Kinase Type 1

Calcium

Cyclic GMP-Dependent Protein Kinases

Cyclic AMP

Phosphatidylinositols

Mitogen-Activated Protein Kinases

Molecular Sequence Data

Isoenzymes

Calmodulin

MAP Kinase Signaling System

Enzyme Inhibitors

Amino Acid Sequence

Paramecium tetraurelia

Kinetics

p38 Mitogen-Activated Protein Kinases

Cell Line

Cells, Cultured

eIF-2 Kinase

Tetradecanoylphorbol Acetate

Protein Kinase C-alpha

Mitogen-Activated Protein Kinase 1

Protein Binding

Substrate Specificity

Cyclic AMP-Dependent Protein Kinase Catalytic Subunits

Mitogen-Activated Protein Kinase Kinases

Mitogen-Activated Protein Kinase 3

Cyclic GMP

Protein Kinase C-delta

Cyclic AMP-Dependent Protein Kinase Type II

Proto-Oncogene Proteins c-akt

Mutation

JNK Mitogen-Activated Protein Kinases

Phosphoproteins

Calcium-Binding Proteins

Blotting, Western

Isoquinolines

Phosphoprotein Phosphatases

Transfection

Peptide T

Binding Sites

Phosphatidylinositol Phosphates

Base Sequence

Serine

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

Cyclic GMP-Dependent Protein Kinase Type I

AMP-Activated Protein Kinases

Androstadienes

Cattle

Adenosine Triphosphate

src-Family Kinases

Cyclic AMP-Dependent Protein Kinase RIalpha Subunit

Recombinant Fusion Proteins

Nucleotides, Cyclic

Protein-Tyrosine Kinases

Chromones

Protamine Kinase

Protein Kinase C-epsilon

Protein Kinase C beta

1-Phosphatidylinositol 4-Kinase

Benzylamines

Rats, Sprague-Dawley

Recombinant Proteins

Cyclic GMP-Dependent Protein Kinase Type II

Cell Membrane

Calcium-Calmodulin-Dependent Protein Kinase Type 4

Cytosol

Morpholines

Apoptosis

RNA, Messenger