Phosphatidylinositol 3 kinases. Medical search

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.

Phosphatidylinositols in which one or more alcohol group of the inositol has been substituted with a phosphate group.

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.

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)

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 group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.

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.

Derivatives of the steroid androstane having two double bonds at any site in any of the rings.

A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol into 1-phosphatidylinositol 3-phosphate.

A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.

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.

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.

Agents that inhibit PROTEIN KINASES.

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)

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.

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.

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.

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.

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.

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.

Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

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.

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.

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.

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.

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.

Established cell cultures that have the potential to propagate indefinitely.

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).

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.

Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.

A group of hydrolases which catalyze the hydrolysis of monophosphoric esters with the production of one mole of orthophosphate. EC 3.1.3.

An enzyme that catalyzes the formation of PHOSPHATIDYLINOSITOL and CMP from CDP-DIACYLGLYCEROL and MYOINOSITOL.

The rate dynamics in chemical or physical systems.

An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction.

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.

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.

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.

A phosphorus-oxygen lyase found primarily in BACTERIA. The enzyme catalyzes the cleavage of a phosphoester linkage in 1-phosphatidyl-1D-myo-inositol to form 1D-myo-inositol 1,2-cyclic phosphate and diacylglycerol. The enzyme was formerly classified as a phosphoric diester hydrolase (EC 3.1.4.10) and is often referred to as a TYPE C PHOSPHOLIPASES. However it is now known that a cyclic phosphate is the final product of this enzyme and that water does not enter into the reaction.

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 non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.

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.

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).

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 lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.

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.

An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

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 class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.

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.

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.

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.

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.

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 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.

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 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 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 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.

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.

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.

A rather large group of enzymes comprising not only those transferring phosphate but also diphosphate, nucleotidyl residues, and others. These have also been subdivided according to the acceptor group. (From Enzyme Nomenclature, 1992) EC 2.7.

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.

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.

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 structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.

An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC 2.7.1.107.

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.

Proteins prepared by recombinant DNA technology.

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 cell line derived from cultured tumor cells.

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 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.

An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21.

Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID.

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.

A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.

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.

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.

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 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 ubiquitous family of proteins that transport PHOSPHOLIPIDS such as PHOSPHATIDYLINOSITOL and PHOSPHATIDYLCHOLINE between membranes. They play an important role in phospholipid metabolism during vesicular transport and SIGNAL TRANSDUCTION.

The parts of a macromolecule that directly participate in its specific combination with another molecule.

A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.

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 non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.

The relationship between the dose of an administered drug and the response of the organism to the drug.

Transport proteins that carry specific substances in the blood or across cell membranes.

An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.

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.

A group of phenyl benzopyrans named for having structures like FLAVONES.

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 phosphatidylinositol 3-kinase subclass that includes enzymes whose specificity is limited to 1-phosphatidylinositol. Members of this class play a role in vesicular transport and in the regulation of TOR KINASES.

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

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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 family of non-receptor, PROLINE-rich protein-tyrosine kinases.

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 family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.

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.

Elements of limited time intervals, contributing to particular results or situations.

A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.

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 lipid phosphatase that acts on phosphatidylinositol-3,4,5-trisphosphate to regulate various SIGNAL TRANSDUCTION PATHWAYS. It modulates CELL GROWTH PROCESSES; CELL MIGRATION; and APOPTOSIS. Mutations in PTEN are associated with COWDEN DISEASE and PROTEUS SYNDROME as well as NEOPLASTIC CELL TRANSFORMATION.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.

A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.

Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.

Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.

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.

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 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.

A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.

A type C phospholipase with specificity towards PHOSPHATIDYLINOSITOLS that contain INOSITOL 1,4,5-TRISPHOSPHATE. Many of the enzymes listed under this classification are involved in intracellular signaling.

A viral oncoprotein originally isolated from a murine T CELL LYMPHOMA infected with the acutely transforming retrovirus AKT8. v-akt protein is the viral homologue of PROTO-ONCOGENE PROTEINS C-AKT.

Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.

Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.

Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.

A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.

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 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.

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.

An enzyme found mostly in plant tissue. It hydrolyzes glycerophosphatidates with the formation of a phosphatidic acid and a nitrogenous base such as choline. This enzyme also catalyzes transphosphatidylation reactions. EC 3.1.4.4.

A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.

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.

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.

A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.

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.

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.

An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

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.

A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.

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.

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.

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.

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.

All of the processes involved in increasing CELL NUMBER including CELL DIVISION.

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.

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.

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.

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.

The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.

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.

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 subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.

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.

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.

A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.

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 class of protein-serine-threonine kinases that was originally found as one of the three types of kinases that phosphorylate GLYCOGEN SYNTHASE. Glycogen synthase kinases along with CA(2+)-CALMODULIN DEPENDENT PROTEIN KINASES and CYCLIC AMP-DEPENDENT PROTEIN KINASES regulate glycogen synthase activity.

Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.

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.

A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.

Four carbon unsaturated hydrocarbons containing two double bonds.

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.

Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.

A phosphoinositide phospholipase C subtype that is structurally defined by the presence of an N-terminal pleckstrin-homology and EF-hand domains, a central catalytic domain, and a C-terminal calcium-dependent membrane-binding domain.

A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.

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 group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.

Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.

A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.

Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.

Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.

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.

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)

Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.

Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes.

A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.

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.

A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.

A mitogen-activated protein kinase kinase with specificity for P38 MITOGEN-ACTIVATED PROTEIN KINASES.

CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.

A serine-threonine kinase that plays important roles in CELL DIFFERENTIATION; CELL MIGRATION; and CELL DEATH of NERVE CELLS. It is closely related to other CYCLIN-DEPENDENT KINASES but does not seem to participate in CELL CYCLE regulation.

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.

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.

Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.

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 biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.

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 mitogen-activated protein kinase kinase with specificity for a subset of P38 MITOGEN-ACTIVATED PROTEIN KINASES that includes MITOGEN-ACTIVATED PROTEIN KINASE 12; MITOGEN-ACTIVATED PROTEIN KINASE 13; and MITOGEN-ACTIVATED PROTEIN KINASE 14.

The phosphoric acid ester of serine.

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.

Compounds containing carbohydrate or glycosyl groups linked to phosphatidylinositols. They anchor GPI-LINKED PROTEINS or polysaccharides to cell membranes.

A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).

Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.

An enzyme catalyzing the transfer of a phosphate group from 3-phospho-D-glycerate in the presence of ATP to yield 3-phospho-D-glyceroyl phosphate and ADP. EC 2.7.2.3.

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.

A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.

Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.

Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.

The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.

A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.

A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.

Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. (1/13288)

The vacuolar protein sorting (VPS) pathway of Saccharomyces cerevisiae mediates transport of vacuolar protein precursors from the late Golgi to the lysosome-like vacuole. Sorting of some vacuolar proteins occurs via a prevacuolar endosomal compartment and mutations in a subset of VPS genes (the class D VPS genes) interfere with the Golgi-to-endosome transport step. Several of the encoded proteins, including Pep12p/Vps6p (an endosomal target (t) SNARE) and Vps45p (a Sec1p homologue), bind each other directly [1]. Another of these proteins, Vac1p/Pep7p/Vps19p, associates with Pep12p and binds phosphatidylinositol 3-phosphate (PI(3)P), the product of the Vps34 phosphatidylinositol 3-kinase (PI 3-kinase) [1] [2]. Here, we demonstrate that Vac1p genetically and physically interacts with the activated, GTP-bound form of Vps21p, a Rab GTPase that functions in Golgi-to-endosome transport, and with Vps45p. These results implicate Vac1p as an effector of Vps21p and as a novel Sec1p-family-binding protein. We suggest that Vac1p functions as a multivalent adaptor protein that ensures the high fidelity of vesicle docking and fusion by integrating both phosphoinositide (Vps34p) and GTPase (Vps21p) signals, which are essential for Pep12p- and Vps45p-dependent targeting of Golgi-derived vesicles to the prevacuolar endosome. (+info)

Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis. (2/13288)

The Met tyrosine kinase - the HGF receptor - induces cell transformation and metastasis when constitutively activated. Met signaling is mediated by phosphorylation of two carboxy-terminal tyrosines which act as docking sites for a number of SH2-containing molecules. These include Grb2 and p85 which couple the receptor, respectively, with Ras and PI 3-kinase. We previously showed that a Met mutant designed to obtain preferential coupling with Grb2 (Met2xGrb2) is permissive for motility, increases transformation, but - surprisingly - is impaired in causing invasion and metastasis. In this work we used Met mutants optimized for binding either p85 alone (Met2xPI3K) or p85 and Grb2 (MetPI3K/Grb2) to evaluate the relative importance of Ras and PI 3-kinase as downstream effectors of Met. Met2xPI3K was competent in eliciting motility, but not transformation, invasion, or metastasis. Conversely, MetP13K/Grb2 induced motility, transformation, invasion and metastasis as efficiently as wild type Met. Furthermore, the expression of constitutively active PI 3-kinase in cells transformed by the Met2xGrb2 mutant, fully rescued their ability to invade and metastasize. These data point to a central role for PI 3-kinase in Met-mediated invasiveness, and indicate that simultaneous activation of Ras and PI 3-kinase is required to unleash the Met metastatic potential. (+info)

Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. (3/13288)

Amyloid fibrils are assemblies of misfolded proteins and are associated with pathological conditions such as Alzheimer's disease and the spongiform encephalopathies. In the amyloid diseases, a diverse group of normally soluble proteins self-assemble to form insoluble fibrils. X-ray fibre diffraction studies have shown that the protofilament cores of fibrils formed from the various proteins all contain a cross-beta-scaffold, with beta-strands perpendicular and beta-sheets parallel to the fibre axis. We have determined the threedimensional structure of an amyloid fibril, formed by the SH3 domain of phosphatidylinositol-3'-kinase, using cryo-electron microscopy and image processing at 25 A resolution. The structure is a double helix of two protofilament pairs wound around a hollow core, with a helical crossover repeat of approximately 600 A and an axial subunit repeat of approximately 27 A. The native SH3 domain is too compact to fit into the fibril density, and must unfold to adopt a longer, thinner shape in the amyloid form. The 20x40-A protofilaments can only accommodate one pair of flat beta-sheets stacked against each other, with very little inter-strand twist. We propose a model for the polypeptide packing as a basis for understanding the structure of amyloid fibrils in general. (+info)

Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. (4/13288)

Interaction between integrin alphavbeta3 and extracellular matrix is crucial for endothelial cells sprouting from capillaries and for angiogenesis. Furthermore, integrin-mediated outside-in signals co-operate with growth factor receptors to promote cell proliferation and motility. To determine a potential regulation of angiogenic inducer receptors by the integrin system, we investigated the interaction between alphavbeta3 integrin and tyrosine kinase vascular endothelial growth factor receptor-2 (VEGFR-2) in human endothelial cells. We report that tyrosine-phosphorylated VEGFR-2 co-immunoprecipitated with beta3 integrin subunit, but not with beta1 or beta5, from cells stimulated with VEGF-A165. VEGFR-2 phosphorylation and mitogenicity induced by VEGF-A165 were enhanced in cells plated on the alphavbeta3 ligand, vitronectin, compared with cells plated on the alpha5beta1 ligand, fibronectin or the alpha2beta1 ligand, collagen. BV4 anti-beta3 integrin mAb, which does not interfere with endothelial cell adhesion to vitronectin, reduced (i) the tyrosine phosphorylation of VEGFR-2; (ii) the activation of downstream transductor phosphoinositide 3-OH kinase; and (iii) biological effects triggered by VEGF-A165. These results indicate a new role for alphavbeta3 integrin in the activation of an in vitro angiogenic program in endothelial cells. Besides being the most important survival system for nascent vessels by regulating cell adhesion to matrix, alphavbeta3 integrin participates in the full activation of VEGFR-2 triggered by VEGF-A, which is an important angiogenic inducer in tumors, inflammation and tissue regeneration. (+info)

The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. (5/13288)

Stimulation of the hepatocyte growth factor (HGF) receptor tyrosine kinase, Met, induces mitogenesis, motility, invasion, and branching tubulogenesis of epithelial and endothelial cell lines in culture. We have previously shown that Gab1 is the major phosphorylated protein following stimulation of the Met receptor in epithelial cells that undergo a morphogenic program in response to HGF. Gab1 is a member of the family of IRS-1-like multisubstrate docking proteins and, like IRS-1, contains an amino-terminal pleckstrin homology domain, in addition to multiple tyrosine residues that are potential binding sites for proteins that contain SH2 or PTB domains. Following stimulation of epithelial cells with HGF, Gab1 associates with phosphatidylinositol 3-kinase and the tyrosine phosphatase SHP2. Met receptor mutants that are impaired in their association with Gab1 fail to induce branching tubulogenesis. Overexpression of Gab1 rescues the Met-dependent tubulogenic response in these cell lines. The ability of Gab1 to promote tubulogenesis is dependent on its pleckstrin homology domain. Whereas the wild-type Gab1 protein is localized to areas of cell-cell contact, a Gab1 protein lacking the pleckstrin homology domain is localized predominantly in the cytoplasm. Localization of Gab1 to areas of cell-cell contact is inhibited by LY294002, demonstrating that phosphatidylinositol 3-kinase activity is required. These data show that Gab1 is an important mediator of branching tubulogenesis downstream from the Met receptor and identify phosphatidylinositol 3-kinase and the Gab1 pleckstrin homology domain as crucial for subcellular localization of Gab1 and biological responses. (+info)

Signals from the Ras, Rac, and Rho GTPases converge on the Pak protein kinase in Rat-1 fibroblasts. (6/13288)

Ras plays a key role in regulating cellular proliferation, differentiation, and transformation. Raf is the major effector of Ras in the Ras > Raf > Mek > extracellular signal-activated kinase (ERK) cascade. A second effector is phosphoinositide 3-OH kinase (PI 3-kinase), which, in turn, activates the small G protein Rac. Rac also has multiple effectors, one of which is the serine threonine kinase Pak (p65(Pak)). Here we show that Ras, but not Raf, activates Pak1 in cotransfection assays of Rat-1 cells but not NIH 3T3 cells. We tested agents that activate or block specific components downstream of Ras and demonstrate a Ras > PI 3-kinase > Rac/Cdc42 > Pak signal. Although these studies suggest that the signal from Ras through PI 3-kinase is sufficient to activate Pak, additional studies suggested that other effectors contribute to Pak activation. RasV12S35 and RasV12G37, two effector mutant proteins which fail to activate PI 3-kinase, did not activate Pak when tested alone but activated Pak when they were cotransfected. Similarly, RacV12H40, an effector mutant that does not bind Pak, and Rho both cooperated with Raf to activate Pak. A dominant negative Rho mutant also inhibited Ras activation of Pak. All combinations of Rac/Raf and Ras/Raf and Rho/Raf effector mutants that transform cells cooperatively stimulated ERK. Cooperation was Pak dependent, since all combinations were inhibited by kinase-deficient Pak mutants in both transformation assays and ERK activation assays. These data suggest that other Ras effectors can collaborate with PI 3-kinase and with each other to activate Pak. Furthermore, the strong correlation between Pak activation and cooperative transformation suggests that Pak activation is necessary, although not sufficient, for cooperative transformation of Rat-1 fibroblasts by Ras, Rac, and Rho. (+info)

Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. (7/13288)

Activation of the extracellularly regulated kinase (ERK) pathway is part of the early biochemical events that follow lipopolysaccharide (LPS) treatment of macrophages or their infection by virulent and attenuated Salmonella strains. Phagocytosis as well as the secretion of invasion-associated proteins is dispensable for ERK activation by the pathogen. Furthermore, the pathways used by Salmonella and LPS to stimulate ERK are identical, suggesting that kinase activation might be solely mediated by LPS. Both stimuli activate ERK by a mechanism involving herbimycin-dependent tyrosine kinase(s) and phosphatidylinositol 3-kinase. Phospholipase D activation and stimulation of protein kinase C appear to be intermediates in this novel pathway of MEK/ERK activation. (+info)

Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Involvement of Jak2 in the stimulation of phosphatidylinositol 3-kinase. (8/13288)

Granulocyte-macrophage colony-stimulating factor (GM-CSF) regulates many of the biological activities of human neutrophils. The signaling pathways via which these effects are mediated are not fully understood. We have shown previously that GM-CSF treatment of human neutrophils activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway and, more specifically, Jak2, STAT3, and STAT5B in neutrophils. GM-CSF also stimulates the activity of the phosphatidylinositol 3-kinase (PI3-kinase) in a tyrosine kinase-dependent manner. Here we report that pretreating the cells with a Jak2 inhibitor (AG-490) abolishes tyrosine phosphorylation of the p85 subunit of PI3-kinase induced by GM-CSF. Furthermore, p85 was found to associate with Jak2, but not with Lyn, in stimulated cells in situ and with its autophosphorylated form in vitro; however, Jak2 did not bind to either of the two Src homology 2 (SH2) domains of the p85 subunit of PI3-kinase. Although STAT5B bound to the carboxyl-terminal SH2 domain of p85, it was absent from the complex containing PI3-kinase and Jak2. These results suggest that stimulation of the activity of PI3-kinase induced by GM-CSF is mediated by Jak2 and that the association between Jak2 and p85 depends on an adaptor protein yet to be identified. (+info)

... phosphatidylinositol 4-kinase beta (PI4KB) phosphatidylinositol 4-kinase 2-alpha (PI4K2A) phosphatidylinositol 4-kinase 2-beta ... Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms phosphatidylinositol ... This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, ... "Protein kinase D regulates vesicular transport by phosphorylating and activating phosphatidylinositol-4 kinase IIIbeta at the ...

https://en.wikipedia.org/wiki/PI4KB

... is caused by gain-of-function mutations in the gene PIK3CD, which stands for phosphatidylinositol 3-kinase, ... Specific p110δ mutants cause stronger binding to membranes and relieve inhibition of the kinase by regulatory proteins. These ... "OMIM: PHOSPHATIDYLINOSITOL 3-KINASE, CATALYTIC, DELTA; PIK3CD". OMIM. Johns Hopkins University. Retrieved December 8, 2018. ... and a kinase domain. Mutations have been identified in multiple domains, although there seems to be a recurrent transition ...

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

Yamaki N, Negishi M, Katoh H (August 2007). "RhoG regulates anoikis through a phosphatidylinositol 3-kinase-dependent mechanism ... Phospholipase D1 and the MAP Kinase activator MLK3. RhoG has been shown to interact with KTN1. GRCh38: Ensembl release 89: ... 22 (3): 330-42. doi:10.1038/sj.onc.1206116. PMID 12545154. Katoh H, Yasui H, Yamaguchi Y, Aoki J, Fujita H, Mori K, Negishi M ( ... Zalcman G, Closson V, Camonis J, Honoré N, Rousseau-Merck MF, Tavitian A, Olofsson B (November 1996). "RhoGDI-3 is a new GDP ...

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

"Entrez Gene: IL1R1 interleukin 1 receptor, type I". Reddy, S A; Huang J H; Liao W S (November 1997). "Phosphatidylinositol 3- ... kinase in interleukin 1 signaling. Physical interaction with the interleukin 1 receptor and requirement in NFkappaB and AP-1 ... Sizemore N, Leung S, Stark GR (1999). "Activation of phosphatidylinositol 3-kinase in response to interleukin-1 leads to ... Reddy SA, Huang JH, Liao WS (1997). "Phosphatidylinositol 3-kinase in interleukin 1 signaling. Physical interaction with the ...

https://en.wikipedia.org/wiki/Interleukin_1_receptor,_type_I

Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2 is a protein that in humans is encoded by the PREX2 ... "Entrez Gene: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor 2". Retrieved 2012-05-11. Rosenfeldt H, ... 572 (1-3): 167-71. doi:10.1016/j.febslet.2004.06.097. PMID 15304342. S2CID 35668920. Berger MF, Hodis E, Heffernan TP, Deribe ... 572 (1-3): 172-6. doi:10.1016/j.febslet.2004.06.096. PMID 15304343. S2CID 31436247. Hernández-Negrete I, Carretero-Ortega J, ...

https://en.wikipedia.org/wiki/PREX2

"Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". The Journal of ... Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the PIK3R2 gene. A recent study ... June 1997). "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking- ... April 1992). "Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 ...

https://en.wikipedia.org/wiki/PIK3R2

It is a large kinase of about 301.66 kDa. ATR belongs to the phosphatidylinositol 3-kinase-related kinase protein family. ATR ... kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment ... Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein ... Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (April 2005). "Rheb binds and regulates the mTOR kinase". Current Biology. 15 ...

https://en.wikipedia.org/wiki/Ataxia_telangiectasia_and_Rad3_related

Metjian A, Roll RL, Ma AD, Abrams CS (1999). "Agonists cause nuclear translocation of phosphatidylinositol 3-kinase gamma. A ... Phosphoinositide 3-kinase regulatory subunit 5 is an enzyme that in humans is encoded by the PIK3R5 gene. PIK3R5 has been shown ... 2005). "p84, a new Gbetagamma-activated regulatory subunit of the type IB phosphoinositide 3-kinase p110gamma". Curr. Biol. 15 ... "Entrez Gene: PIK3R5 phosphoinositide-3-kinase, regulatory subunit 5, p101". Johnson C, Marriott SJ, Levy LS (2007). " ...

https://en.wikipedia.org/wiki/PIK3R5

1995). "The activation of phosphatidylinositol 3-kinase by Ras". Curr. Biol. 4 (9): 798-806. doi:10.1016/S0960-9822(00)00177-9 ... 48 (4): 950-3. PMID 3276402. Hirai H, Kobayashi Y, Mano H, et al. (1987). "A point mutation at codon 13 of the N-ras oncogene ... 5 (3): 582-5. doi:10.1128/mcb.5.3.582. PMC 366752. PMID 3887133. Brown R, Marshall CJ, Pennie SG, Hall A (1984). "Mechanism of ... 299 (5879): 171-3. Bibcode:1982Natur.299..171M. doi:10.1038/299171a0. PMID 6287287. S2CID 4342747. Shimizu K, Goldfarb M, ...

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

Sidorenko SP, Law CL, Chandran KA, Clark EA (1995). "Human spleen tyrosine kinase p72Syk associates with the Src-family kinase ... "Thymocyte activation induces the association of phosphatidylinositol 3-kinase and pp120 with CD5". Eur. J. Immunol. 27 (3): 679 ... Jordan P, Heid H, Kinzel V, Kübler D (1995). "Major cell surface-located protein substrates of an ecto-protein kinase are ... 425 (3): 401-6. doi:10.1016/S0014-5793(98)00269-5. PMID 9563502. Matsui M, Breau WC, Iwasaki S, Hagiwara S, Tamai Y, Mori C, ...

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

Polo-like kinase phosphosites 1 (Plk1) at positions 336-342 aa and 351-357 aa. Ser/Thr residues are phosphorylated by the ... Phosphatidylinositol 3-kinase related kinase (PIKK) phosphorylation site at position 238-244 aa. Casein kinase (CK1) ... Ser/Thr residues are phosphorylated by the kinase. Two NEK2 phosphorylation sites at positions 415-420 bp and 423-428 aa. Table ... Glycogen synthase kinase-3 (GSK3) phosphorylation site at position 234-241 aa. ...

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

... also known as PI3-kinase regulatory subunit 4 or PI3-kinase p150 subunit or phosphoinositide 3-kinase adaptor protein, or VPS15 ... Substrate presentation by phosphatidylinositol transfer protein to the p150.Ptdins 3-kinase complex". J. Biol. Chem. 272 (4): ... an adaptor protein for the human phosphatidylinositol (PtdIns) 3-kinase. ... J. 417 (3): 747-55. doi:10.1042/BJ20081865. PMC 2652830. PMID 18957027. Portal: Biology v t e (Genes on human chromosome 3, EC ...

https://en.wikipedia.org/wiki/PIK3R4

March 2003). "MTA1 interacts with MAT1, a cyclin-dependent kinase-activating kinase complex ring finger factor, and regulates ... Interaction of estrogen receptor alpha with phosphatidylinositol 3-OH kinase". Steroids. 67 (12): 935-939. doi:10.1016/S0039- ... Fes tyrosine kinase, heat shock transcription factor Hsf1, and the aryl hydrocarbon receptor". Cell Stress & Chaperones. 1 (4 ... monophosphate-dependent protein kinase". Endocrinology. 149 (9): 4336-4345. doi:10.1210/en.2008-0037. PMID 18499756. Wong CW, ...

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

The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an ... Izuhara K, Harada N (1997). "Interleukin-4 activates two distinct pathways of phosphatidylinositol-3 kinase in the same cells ... Potential role of JAK kinases". J. Biol. Chem. 270 (48): 28527-30. doi:10.1074/jbc.270.48.28527. PMID 7499365. Patti ME, Sun XJ ... and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. ...

https://en.wikipedia.org/wiki/IRS2

... a new MAP kinase-activated protein kinase, isolated by a novel expression screening method for identifying protein kinase ... "Involvement of phosphatidylinositol 3-kinase, but not RalGDS, in TC21/R-Ras2-mediated transformation". J. Biol. Chem. 277 (12 ... Li W, Han M, Guan KL (April 2000). "The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex ... Ramírez de Molina A, Penalva V, Lucas L, Lacal JC (2002). "Regulation of choline kinase activity by Ras proteins involves Ral- ...

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

2005). "Distinct roles of the receptor tyrosine kinases Tie1 and Tie2 in blood vessel formation". Cell. 123 (2): 291-304. doi: ... Kumar, P; Amin, MA; Harlow, LA; Polverini, PJ; Koch, AE (2003). "Src and phosphatidylinositol 3-kinase mediate soluble E- ... 1995). "Distinct roles of the receptor tyrosine kinases Tie1 and Tie2 in blood vessel formation". Nature. 376 (6535): 70-74. ... and modulate the activity of focal adhesion kinase (FAK). Endostatin is a 20 kDa fragment of collagen XVIII. The major role of ...

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

"Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and ... It was shown that the activation occurs through phosphatidylinositol 3-kinase. In the developing nervous system AKT is a ... Chan TO, Rittenhouse SE, Tsichlis PN (2000). "AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by ... "Complex formation and cooperation of protein kinase C theta and Akt1/protein kinase B alpha in the NF-kappa B transactivation ...

https://en.wikipedia.org/wiki/AKT1

Kihara A, Kabeya Y, Ohsumi Y, Yoshimori T (April 2001). "Beclin-phosphatidylinositol 3-kinase complex functions at the trans- ... April 2004). "Ceramide-mediated macroautophagy involves inhibition of protein kinase B and up-regulation of beclin 1". The ... April 2009). "Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3- ... kinase complex". Nature Cell Biology. 11 (4): 468-76. doi:10.1038/ncb1854. PMC 2664389. PMID 19270693. Valente G, Morani F, ...

https://en.wikipedia.org/wiki/BECN1

"PIP5K1A phosphatidylinositol-4-phosphate 5-kinase, type I, alpha [Homo sapiens (human)". Entrez Gene. PSD4 pleckstrin and Sec7 ... PIK3R2 and PIP5K1A are two kinases that phosphorylate Phosphatidylinositol (PIP) providing PSD4 with substrates for its GTP ... PIK3R2 and PIP5K1A are two kinases that create substrates for PSD4. PSD4 (Pleckstrin and Sec7 Domain containing 4) is a GEF ( ... MHC class II is also expressed on group 3 innate lymphoid cells. Having MHC class II molecules present proper peptides that are ...

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

"Cloning of a novel phosphatidylinositol kinase-related kinase: characterization of the human SMG-1 RNA surveillance protein". J ... Serine/threonine-protein kinase SMG1 is an enzyme that in humans is encoded by the SMG1 gene. SMG1 belongs to the ... The protein has kinase activity and is thought to function in NMD by phosphorylating the regulator of nonsense transcripts 1 ... Sanchez P, De Carcer G, Sandoval IV, Moscat J, Diaz-Meco MT (1998). "Localization of atypical protein kinase C isoforms into ...

https://en.wikipedia.org/wiki/SMG1

... acts as a negative regulator of mTOR, a serine/threonine kinase that regulates a variety of cellular functions such as ... "REDD1 integrates hypoxia-mediated survival signaling downstream of phosphatidylinositol 3-kinase". Oncogene. 24 (7): 1138-49. ... 1 (3): 287-92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614. Kim JR, Lee SR, Chung HJ, Kim S, Baek SH, Kim JH, ... 11 (3): 422-35. doi:10.1101/gr.GR1547R. PMC 311072. PMID 11230166. Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann ...

https://en.wikipedia.org/wiki/DDIT4

"PI3 Kinase Disease , NIH: National Institute of Allergy and Infectious Diseases". www.niaid.nih.gov. Retrieved 2017-06-10. " ... "PIK3CD phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [Homo sapiens (human)] - Gene - NCBI". www.ncbi. ... a mutation in phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform is the reason for this condition ( ...

https://en.wikipedia.org/wiki/Activated_PI3K_delta_syndrome

"The West Nile Virus Capsid Protein Blocks Apoptosis through a Phosphatidylinositol 3-Kinase-Dependent Mechanism". Journal of ... 20 (3): 326-7. PMID 15532939. "General Questions About West Nile Virus". www.cdc.gov. 19 October 2017. Archived from the ... 3 (1): 13-22. doi:10.1038/nrmicro1067. PMID 15608696. S2CID 4150641. Suthar, Mehul S.; Diamond, Michael S.; Gale, Michael Jr. ( ... 3 October 2017. Retrieved 28 March 2019. "Vertebrate Ecology". West Nile Virus. Division of Vector-Borne Diseases, CDC. 30 ...

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

The age-1 gene encodes the catalytic subunit of class-I phosphatidylinositol 3-kinase (PI3K). A decade after Johnson's ... and tyrosine kinase-related pathways. They then used drugs known to target the identified pathways and showed these drugs kill ... 22 (3-4): 279-286. doi:10.1016/0047-6374(83)90082-9. PMID 6632998. S2CID 6870538. Friedman DB, Johnson TE (1988). "A mutation ... Bibcode:2020NatCo..11.3570T. doi:10.1038/s41467-020-17312-3. ISSN 2041-1723. PMC 7366647. PMID 32678081. Text and images are ...

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

"DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene ... "Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit". J. Biol. Chem. 272 ( ... "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". J. ... DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene ...

https://en.wikipedia.org/wiki/DNA-PKcs

"Protein kinase C alpha phosphorylates and negatively regulates diacylglycerol kinase zeta". The Journal of Biological Chemistry ... The phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (the HUGO-approved official symbol = PIK3CA; HGNC ... Li W, Han M, Guan KL (April 2000). "The leucine-rich repeat protein SUR-8 enhances MAP kinase activation and forms a complex ... Prasad KV, Kapeller R, Janssen O, Repke H, Duke-Cohan JS, Cantley LC, Rudd CE (December 1993). "Phosphatidylinositol (PI) 3- ...

https://en.wikipedia.org/wiki/P110α

It codes for an isozyme of pyruvate dehydrogenase kinase. This gene is a member of the PDK/BCKDK protein kinase family and ... This is done through a proposed phosphatidylinositol 3-kinase (PI3K)-dependent pathway. In fact, even when cells are exposed to ... Kwon HS, Huang B, Unterman TG, Harris RA (Apr 2004). "Protein kinase B-alpha inhibits human pyruvate dehydrogenase kinase-4 ... Pyruvate dehydrogenase lipoamide kinase isozyme 4, mitochondrial is an enzyme that in humans is encoded by the PDK4 gene. ...

https://en.wikipedia.org/wiki/PDK4

CT10 regulator of kinase (Crk) is also known as the breast cancer anti-oestrogen resistance protein. It plays a role in both ... Boudot C, Kadri Z, Petitfrère E, Lambert E, Chrétien S, Mayeux P, Haye B, Billat C (October 2002). "Phosphatidylinositol 3- ... This leads to the activation of c-Jun N-terminal kinase(JNK) as part of the JNK signaling pathway. Upon stimulation by growth ... It mediates the interaction between receptor tyrosine kinases (RTKs) and non-RTK receptors serving as the gateway into the cell ...

https://en.wikipedia.org/wiki/GAB2

2003). "Phosphatidylinositol 3-kinases in carcinoembryonic antigen-related cellular adhesion molecule-mediated internalization ... 49 (3): 623-37. doi:10.1046/j.1365-2958.2003.03591.x. PMID 12864848. S2CID 12071872. Schmitter T, Agerer F, Peterson L, et al ... 158 (3): 996-1004. CiteSeerX 10.1.1.657.2780. doi:10.1016/0006-291X(89)92821-0. PMID 2537643. Watt SM, Fawcett J, Murdoch SJ, ... Carcinoembryonic antigen-related cell adhesion molecule 3 (CEACAM3) also known as CD66d (Cluster of Differentiation 66d), is a ...

https://en.wikipedia.org/wiki/CEACAM3

One key pathway triggered by IFN-γ binding IFNGRs is the Janus Kinase and Signal Transducer and Activator of Transcription ... The JAK proteins also lead to the activation of phosphatidylinositol 3-kinase (PI3K). PI3K leads to the activation of protein ... kinase C-δ (PKC-δ) which phosphorylates the amino acid serine in STAT1 transcription factors. The phosphorylation of the serine ...

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

Src-family tyrosine kinases in activation of ERK-1 and p85/p110-phosphatidylinositol 3-kinase by G/CCKB receptors.". J. Biol. ... CysLT (1, 2) • LTB4 (1, 2) • FPRL1 • OXE • Prostaglandin (DP (1, 2), EP (1, 2, 3, 4), FP) • Prostaciklin • Tromboksan ... Adrenomedulin • Mirisni • Opsin (3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH) • Proteazom-aktivirani (1, 2, 3, 4) • SREB (1, 2, 3) ... Žučna kiselina • Kanabinoidni (CB1, CB2, GPR (18, 55, 119)) • EBI2 • Estrogen • Slobodna masna kiselina (1, 2, 3, 4) • Laktat ...

https://sh.wikipedia.org/wiki/Holecistokininski_receptor_B

Insulin Augmentation of 17α-Hydroxylase Activity Is Mediated by Phosphatidyl Inositol 3-Kinase But Not Extracellular Signal- ... Regulated Kinase-1/2 in Human Ovarian Theca Cells. Endocrinology. January 2004, 145 (1): 175-183. doi:10.1210/en.2003-0329.. ... MODY 1（英语：MODY 1） 2（英语：MODY 2） 3（英语：MODY 3） 4（英语：MODY 4） 5（英语：MODY 5） 6（英语：MODY 6） ... doi:10.1093/humupd/7.1.3.. *^ 26.0 26.1 26.2 Strauss JF. Some new thoughts on the pathophysiology and genetics of polycystic ...

https://zh.wikipedia.org/wiki/多囊卵巢綜合症

... like protein kinase, proliferating cell nuclear antigen (PCNA)-like group, two serine/threonine(S/T) kinases and their adaptors ... Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)- ... the stress-activated protein kinase, c-Jun N-terminal kinase (JNK), phosphorylates SIRT6 on serine 10 in response to double- ... First, two kinases, ATM and ATR are activated within 5 or 6 minutes after DNA is damaged. This is followed by phosphorylation ...

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

2000). «Differential regulation of the phosphatidylinositol 3-kinase/Akt and p70 S6 kinase pathways by the alpha(1A)-adrenergic ... CysLT (1, 2) · LTB4 (1, 2) · FPRL (1, 2, 3) · OXE · Prostaglandina (DP (1, 2), EP (1, 2, 3, 4), FP) · Prostaciclina · ... ADCYAP1R1 · Caderina (1, 2, 3) · Calcitonina · CALCRL · CD97 · EMR (1, 2, 3) · Glucagon (GR, GIPR, GLP1R, GLP2R) · Hormônio ... Sensor de cálcio · GABA B (1, 2) · Glutamato (Metabotrópico de glutamato (1, 2, 3, 4, 5, 6, 7, 8)) · GPRC6A · GPR (156, 158, ...

https://pt.wikipedia.org/wiki/Receptor_adrenérgico_alfa_1A

tirosina kinase transmembran (TrkA) dengan massa 140 kDa.. Kedua pencerap ini berperan dalam kelainan saraf, penurunan imunitas ... Phosphatidylinositol 3-kinase and Akt protein kinase are necessary and sufficient for the survival of nerve growth factor- ... C5a · CCL2 · CCL5 · GSM-CSF · LPS · MCP-1 · IL-1 · IL-2 · IL-3 · IL-4 · IL-5 · IL-6 · IL-8 · IL-10 · IL-12 · IL-13 · IL-15 · IL ... AP-1 · C/EBP-α · β · NF-κB · FLIP · STAT · 1 · 2 · 3 · 4 · 5 · 6 ...

https://id.wikipedia.org/wiki/Faktor_pertumbuhan_saraf

Antiviral and antiproliferative effects specific to type I IFNs result from p38 MAP kinase signaling. The phosphatidylinositol ... Type I IFNs further activate p38 mitogen-activated protein kinase (MAP kinase) to induce gene transcription. ... Production of protein kinase R, for example, can be disrupted in cells infected with JEV. Some viruses escape the anti-viral ... In response to interferon, cells produce large amounts of an enzyme known as protein kinase R (PKR). This enzyme phosphorylates ...

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

Testis-Specific Serine Kinase 6), NT5DC2 (Cytosolic 5'-nucleotidase), PITPNM2 (Membrane-associated phosphatidylinositol ... miR-137 has also been shown to directly inhibits CDK6 (Cyclin-dependent kinase 6) expression and decreases the level of ... Serine/threonine-protein kinase D3). Neault et al. recently identified miR-137 as a senescence effector miRNA induced by ... 52 (3): 1193-1199. doi:10.1167/iovs.10-5272. PMID 21051724. Tarantino C, Paolella G, Cozzuto L, et al. (September 2010). "miRNA ...

https://en.wikipedia.org/wiki/MiR-137

"The Src family kinase Hck interacts with Bcr-Abl by a kinase-independent mechanism and phosphorylates the Grb2-binding site of ... "Stem cell factor induces phosphatidylinositol 3'-kinase-dependent Lyn/Tec/Dok-1 complex formation in hematopoietic cells". ... Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ... Agami R, Shaul Y (April 1998). "The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a ...

https://en.wikipedia.org/wiki/ABL_(gene)

... 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). ... Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)P2) is a minor phospholipid component of cell membranes, yet an important ... A phosphatidylinositol lipids system, lamellipodin, and Ena/VASP regulate dynamic morphology of multipolar migrating cells in ...

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

Bhargavi V, Chari VB, Singh SS (1998). "Phosphatidylinositol 3-kinase binds to profilin through the p85 alpha subunit and ... 229 (3): 621-8. doi:10.1111/j.1432-1033.1995.tb20506.x. PMID 7758455. Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, ... 46 (3): 559-67. PMC 1683621. PMID 1968707. "Entrez Gene: PFN1 profilin 1". Wu CH, Fallini C, Ticozzi N, Keagle PJ, Sapp PC, ... 36 (3): 1602.e17-27. doi:10.1016/j.neurobiolaging.2014.10.032. PMC 4357530. PMID 25499087. Yayoshi-Yamamoto S, Taniuchi I, ...

https://en.wikipedia.org/wiki/Profilin_1

... and protein kinase C activity. This gene encodes an enzyme which regulates the amount of phosphatidylinositol available for ... and the cytoplasmic side of the endoplasmic reticulum where it functions in phosphatidylinositol biosynthesis. Two genes ... synthetase and phosphatidylinositol synthase activity levels in the regulation of cellular phosphatidylinositol content". The ... 67 (5): 2200-3. doi:10.1046/j.1471-4159.1996.67052200.x. hdl:2027.42/65959. PMID 8863531. S2CID 2805319. Human CDS1 genome ...

https://en.wikipedia.org/wiki/CDS1_(gene)

Leitges M, Gimborn K, Elis W, Kalesnikoff J, Hughes MR, Krystal G, Huber M (June 2002). "Protein kinase C-delta is a negative ... This catalytic domain is flanked on the N-terminal side by the PH-like domain that binds phosphatidylinositol-3,4,5- ... Zhang S, Broxmeyer HE (January 1999). "p85 subunit of PI3 kinase does not bind to human Flt3 receptor, but associates with SHP2 ... Dunant NM, Wisniewski D, Strife A, Clarkson B, Resh MD (May 2000). "The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 ...

https://en.wikipedia.org/wiki/INPP5D

... is an inhibitor of phosphatidylinositol-3-kinase (PI3K) with inhibitory activity predominantly against PI3K-α and ... "NDA 209936, Multisciplinary Review document, chapter 3" (PDF). www.fda.gov. Bayer AG (17 May 2017). "Bayer News Release" (PDF ... Phosphoinositide 3-kinase inhibitors, Morpholines, Bayer brands, Pyrimidines). ...

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

"A rapid cytoplasmic mechanism for PI3 kinase regulation by the nuclear thyroid hormone receptor, TRβ, and genetic evidence for ... mechanism for non-genomic signaling through the nuclear thyroid hormone receptor TRβ involves the phosphatidylinositol 3-kinase ... 11 (3): 1003-13. doi:10.1002/j.1460-2075.1992.tb05139.x. PMC 556541. PMID 1312460. Escriva H, Safi R, Hänni C, Langlois MC, ... 2 (1): 3. doi:10.1186/2041-9139-2-3. PMC 3038971. PMID 21291545. Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, ...

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

"HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3- ... kinase/AKT/cyclic nucleoside phosphodiesterase pathway". FASEB Journal. 15 (2): 483-91. doi:10.1096/fj.00-0354com. PMID ... cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene. This gene is a member ... 3 (11): 1093-101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747. Millar JK, Pickard BS, Mackie S, James R, Christie S, Buchanan ...

https://en.wikipedia.org/wiki/PDE4B

The reception of IFNγ activates Janus kinase 1, resulting in the stimulation of its association with Sxn8 above standard ... the PX domain main function is to target SNX8 mainly to early endosomes and other membranes rich in phosphatidylinositol 3- ... 135 and 148 as residues directly related to phosphatidylinositol 3-phosphate since being specific binding sites, constituting a ... SNX8 acts as an adaptor or scaffolding protein by permitting the recruitment of the inhibitor of nuclear factor-kappa-B kinase ...

https://en.wikipedia.org/wiki/SNX8

... which codifies the regulating alpha subunit of phosphatidylinositol 3-kinase. This mutation can alter the PI3K/AKT/mTOR signal ...

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

"Entrez Gene: Phosphoinositide kinase, FYVE finger containing". Shisheva A, Sbrissa D, Ikonomov O (January 1999). "Cloning, ... September 2006). "Fab1 phosphatidylinositol 3-phosphate 5-kinase controls trafficking but not silencing of endocytosed ... Yamamoto A, DeWald DB, Boronenkov IV, Anderson RA, Emr SD, Koshland D (May 1995). "Novel PI(4)P 5-kinase homologue, Fab1p, ... PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene. The ...

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

RGS domains in the G protein-coupled receptor kinases are able to bind to Gq family α-subunits, but do not accelerate their GTP ... PH for phosphatidylinositol-binding (InterPro: IPR001849), and GGL (G protein gamma subunit-like) for binding G protein beta ... 86 (3): 445-52. doi:10.1016/S0092-8674(00)80117-8. PMID 8756726. S2CID 12427406. Koelle MR, Horvitz HR (January 1996). "EGL-10 ...

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

Rapley J, Nicolas M, Groen A, Regue L, Bertran MT, Caelles C, Avruch J, Roig J (2008). "The NIMA-family kinase Nek6 ... "Inhibition of the mitotic kinesin Eg5 up-regulates Hsp70 through the phosphatidylinositol 3-kinase/Akt pathway in multiple ... Bishop JD, Han Z, Schumacher JM (2005). "The Caenorhabditis elegans Aurora B kinase AIR-2 phosphorylates and is required for ... Blangy A, Arnaud L, Nigg EA (1997). "Phosphorylation by p34cdc2 protein kinase regulates binding of the kinesin-related motor ...

https://en.wikipedia.org/wiki/Kinesin-like_protein_KIF11

"Binding of the PX domain of p47phox to phosphatidylinositol 3,4-bisphosphate and phosphatidic acid is masked by an ... However some of them bind to phosphatidic acid, PtdIns(3,4)P2, PtdIns(3,5)P2, PtdIns(4,5)P2, and PtdIns(3,4,5)P3. The PX-domain ... PX domains interact primarily with PtdIns(3)P lipids. ... and phosphoinositide-3-kinases. The PX domain is structurally ... and PtdIns 3-kinases: binding partners of SH3 domains?". Protein Sci. 5 (11): 2353-7. doi:10.1002/pro.5560051122. PMC 2143296. ...

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

Further reading: function of protein kinase C The Gαq / Gα11 (Q209L) mutation is associated with the development of uveal ... PLC-β in turn hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to diacyl glycerol (DAG) and inositol trisphosphate (IP3 ... Second messenger system G protein-coupled receptor Heterotrimeric G protein Phospholipase C Calcium signaling Protein kinase C ... PLC-β then cleaves a specific plasma membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol ( ...

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

1997). "Kinase suppressor of Ras is ceramide-activated protein kinase". Cell. 89 (1): 63-72. doi:10.1016/S0092-8674(00)80183-X ... as an effector phosphorylates phosphatidylinositol bisphosphate (PIP2) to produce phosphatidylinositol (3,4,5)-trisphosphate ( ... Sph is also known to interact with protein targets such as the protein kinase H homologue (PKH) and the yeast protein kinase ( ... A specific protein kinase phosphorylates 14-3-3, otherwise known as sphingosine-dependent protein kinase 1 (SDK1), only in the ...

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

Activatory motifs (ITAMs) bind kinases, such as Syk family kinases (e.g. ZAP70 for T-cell receptor) that phosphorylate a range ... SHP2 and the phosphatidylinositol phosphatase SHIP-1. The phosphatases can attenuate the signal by dephosphorylating a broad ... "Suboptimal cross-linking of antigen receptor induces Syk-dependent activation of p70S6 kinase through protein kinase C and ... If the kinase is associated with an NTR, aggregation brings two or more SFK into close proximity, which allows them to ...

https://en.wikipedia.org/wiki/Non-catalytic_tyrosine-phosphorylated_receptor

"Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". J. Biol. Chem. 269 ( ... Pratt RL, Kinch MS (October 2002). "Activation of the EphA2 tyrosine kinase stimulates the MAP/ERK kinase signaling cascade". ... "Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". J. Biol. Chem. 269 ( ... an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases". Mol. Cell. Biol. 10 (12): 6316- ...

https://en.wikipedia.org/wiki/EPH_receptor_A2

"Association with the SRC family tyrosyl kinase LYN triggers a conformational change in the catalytic region of human cAMP- ... "HIV-1 Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3- ... kinase/AKT/cyclic nucleoside phosphodiesterase pathway" (PDF). FASEB Journal. 15 (2): 483-91. doi:10.1096/fj.00-0354com. PMID ... cAMP-specific 3',5'-cyclic phosphodiesterase 4A is an enzyme that in humans is encoded by the PDE4A gene. The protein encoded ...

https://en.wikipedia.org/wiki/PDE4A

In contrast, TORC2 phosphorylates and activates AKT, a key kinase involved in cell growth and apoptosis. Guan and his team are ... In addition, they are studying the mechanism of mTOR activation by the phosphatidyl inositol 3-kinase (PI3K). The second ... Guan has made seminal contributions in the fields of protein tyrosine phosphatase, Mitogen-Activated Protein (MAP) kinase, and ... For example, TORC1 phosphorylates the ribosomal S6 kinase (S6K), thereby regulating translation and cell growth. ...

https://en.wikipedia.org/wiki/Kun-Liang_Guan

... is involved in phosphatidylinositol signaling pathways. This enzyme removes the phosphate group at position 4 of the ... Zhang X, Majerus PW (April 1998). "Phosphatidylinositol signalling reactions". Seminars in Cell & Developmental Biology. 9 (2 ... "The inositol polyphosphate 4-phosphatase forms a complex with phosphatidylinositol 3-kinase in human platelet cytosol". ... EC 3.1.3, All stub articles, Human chromosome 4 gene stubs). ... inositol ring from inositol 3,4-bisphosphate and phosphate ...

https://en.wikipedia.org/wiki/INPP4B

... suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon ... 391 (3): 1483-9. doi:10.1016/j.bbrc.2009.12.098. PMID 20034472. Feng R, Chen X, Yu Y, Su L, Yu B, Li J, Cai Q, Yan M, Liu B, ... 379 (3): 726-31. doi:10.1016/j.bbrc.2008.12.098. PMID 19116145. Harnprasopwat R, Ha D, Toyoshima T, Lodish H, Tojo A, Kotani A ... VEGF-A protein production is reduced as mir-126 binds to the 3' untranslated region of the VEGF-A mRNA. IRS-1 inhibiting the ...

https://en.wikipedia.org/wiki/Mir-126

... N Engl J Med. 2018 Nov 22;379(21):2052-2062. doi: 10.1056/ ...

https://pubmed.ncbi.nlm.nih.gov/30462943/

A novel mechanism of regulation of phosphatidylinositol 3 -kinase: Tyrosine phosphorylation of p85 residue 688. ...

https://www.proquest.com/openview/fec7e7f58ca708d7250bee303a94d7a6/1?pq-origsite=gscholar&cbl=18750&diss=y

Phosphatidylinositol 3-Kinases [D08.811.913.696.620.500]. *Phosphatidylinositol-4-Phosphate 3-Kinase [D08.811.913.696.620.500. ... "Phosphatidylinositol-4-Phosphate 3-Kinase" is a descriptor in the National Library of Medicines controlled vocabulary ... Phosphatidylinositol-4-Phosphate 3-Kinase*Phosphatidylinositol-4-Phosphate 3-Kinase. *Phosphatidylinositol 4 Phosphate 3 Kinase ... A phosphatidylinositol 3-kinase that catalyzes the conversion of 1-phosphatidylinositol 4-phosphate into phosphatidylinositol 3 ...

https://connects.catalyst.harvard.edu/Profiles/display/Concept/Phosphatidylinositol-4-Phosphate%203-Kinase

A Prospective Multicenter Phase 2 Study of the Chemotherapy-Free Combination of the Intravenous Phosphatidylinositol-3-Kinase ( ... A Prospective Multicenter Phase 2 Study of the Chemotherapy-Free Combination of the Intravenous Phosphatidylinositol-3-Kinase ( ... Not sure for Histologically confirmed follicular lymphoma grade 1, 2 or 3A with a biopsy performed inclusion criteria 3 ... Step 3 Enroll in the clinical study If you are confirmed eligible after full screening, you will be required to understand and ...

https://www.centerwatch.com/clinical-trials/listings/301027/a-prospective-multicenter-phase-2-study-of-the-chemotherapy-free-combination-of-the-intravenous-phosphatidylinositol-3-kinase-pi3k-inhibitor-copanlisib-in-combination-with-obinutuzumab-in-patients-with-previously-untreated-follicular-lymphoma-fl-and-a-hig/

Results show that cannabinoids protect astrocytes from ceramide-induced apoptosis via stimulation of the phosphatidylinositol 3 ... kinase/protein kinase B pathway, the first evidence for an ... regulated kinase and the inhibition of protein kinase B ... The CB1 Cannabinoid Receptor Is Coupled to the Activation of c-Jun N-Terminal Kinase. *D. Rueda, I. Galve-Roperh, A. Haro, M. ... The CB1 cannabinoid receptor is coupled to the activation of protein kinase B/Akt.. *T. Gómez del Pulgar, G. Velasco, M. Guzmán ...

https://www.semanticscholar.org/paper/Cannabinoids-Protect-Astrocytes-from-Apoptosis-the-Pulgar-Ceballos/1480c036de3905cdd0da048288ce106457c57727?p2df

Brutons tyrosine kinase (BTK) function is important to the development and expansion of chronic lymphocytic leukemia (CLL). ... The phosphatidylinositol-3-kinase (PI3K) signaling pathway is an integral part of the BCR signaling machinery and its activity ... Moreover, the decreased phosphorylation of the BCR-proximal kinases LYN, SYK and BTK indicates that BCR signaling is ... The prolonged survival of CLL cells is in part associated with defective apoptosis triggered by the phosphatidylinositol 3- ...

https://haematologica.org/article/view/haematol.2021.279924

IGF-I, insulin-like growth factor 1; IGF-IR, IGF-1 receptor; PI3K, phosphatidylinositol-3 kinase; Bcl, B-cell lymphoma; FADD, ... Effects of lactic acid bacteria on cardiac apoptosis are mediated by activation of the phosphatidylinositol-3 kinase/AKT ... activation of the phosphatidylinositol-3 kinase/Akt (PI3K/AKT) pathway, and it is considered to prevent myocyte apoptosis (17 ... p38 mitogen activated protein kinase activation and apoptosis. Diabetes Obes Metab. 7:448-454. 2005. View Article : Google ...

https://www.spandidos-publications.com/10.3892/ijmm.2014.2021?text=abstract

... showing that PI3-kinase is not involved in the activation of p38 MAP kinase. Data showed that PI3-kinase plays an essential ... PI3-kinase) inhibitors. The p38 mitogen-activated protein (MAP) kinase was activated at 0.5 to 3 h after SAAD, followed by ... The Essential Role of Phosphatidylinositol 3-Kinase and of p38 Mitogen-Activated Protein Kinase Activation in the Antioxidant ... The Essential Role of Phosphatidylinositol 3-Kinase and of p38 Mitogen-Activated Protein Kinase Activation in the Antioxidant ...

https://molpharm.aspetjournals.org/content/58/5/1017.short

Investigation of phosphatidylinositol-3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) activation Chiu, ... Investigation of phosphatidylinositol-3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) activation ... hemopoietic cell lines FDC-P1 and BAF-3 cells. Also, we used a human embryonic kidney cell line, HEK 293. With the use of ... hemopoietic cell lines FDC-P1 and BAF-3 cells. Also, we used a human embryonic kidney cell line, HEK 293. With the use of ...

https://open.library.ubc.ca/soa/cIRcle/collections/ubctheses/831/items/1.0090096

Life Chemicals designed PI3K screening compound library against Phosphatidylinositol 3-kinase, a promising therapeutic anti- ... Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase known to be a promising therapeutic target for cancer. PI3K is an ... Dysregulation of this signaling pathway (PI3K/PDK1/Akt (also known as protein kinase B) has been found in a variety of cancer ... The products of PI3K activity recruit PDK1 and Akt Ser/Thr kinases to the plasma membrane where they are activated, transducing ...

https://lifechemicals.com/screening-libraries/targeted-and-focused-screening-libraries/kinase-sharp-aimed-targeted-libraries/phosphatidylinositol-3-kinase-

A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose ... A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose ... A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose ...

https://profiles.umassmed.edu/display/75025

PI3K activates AKT, serum/glucocorticoid regulated kinase (SGK), phosphoinositide-dependent kinase 1 (PDK1), mammalian target ... PI3K is a major signaling hub downstream of human epidermal growth factor receptor (HER)2 and other receptor tyrosine kinases. ... Mutations in genes that constitute the phosphatidylinositol 3-kinase (PI3K) pathway occur in >70% of breast cancers. ... liver kinase B1; PDK1, phosphoinositide-dependent kinase 1; PI3K, phosphatidylinositol 3-kinase; PIP1, phosphatidylinositol ...

https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr3039

The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and ... 3)/T(4) or fatal). In conclusion, we observed a significant association between PIK3C2B and prostate cancer risk, especially ... Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer. ... The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and ...

https://www.ndph.ox.ac.uk/publications/60698

Western blotting was used to investigate the effect of EGFR stimulation or inhibition as well as phosphatidylinositol 3-kinase ... PI3K) inhibition on mitogen activated protein kinase (MAPK) signaling. Rescue experiments were performed by stable transfection ... From: Phosphatidylinositol 3-Kinase dependent upregulation of the epidermal growth factor receptor upon Flotillin-1 depletion ...

https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-13-575/figures/3

... phosphatidylinositol 5-phosphate 4-kinases (PIP4K), which generate PI(4,5)P2 by phosphorylating phosphatidylinositol 5- ... Phosphatidylinositol 5-phosphate 4-kinase regulates early endosomal dynamics during clathrin-mediated endocytosis Kumari ... Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development ... P2 is synthesized is through phosphorylation of PI4P at position 5 by the activity of phosphatidylinositol 4-phosphate 5-kinase ...

https://journals.biologists.com/jcs/article/130/13/2119/56173/Phosphatidylinositol-5-phosphate-4-kinase

Order Assay kit for human Phosphatidylinositol 3 kinases 2a ELISA 01014458801 at Gentaur kit for Phosphatidylinositol 3 kinases ... The product Assay kit for human Phosphatidylinositol 3 kinases 2a (ELISA) is intended to be used for research purposes only. It ... The product Assay kit for human Phosphatidylinositol 3 kinases 2a (ELISA) should be kept between two and eight degrees Celsius ... the antigen and its analogues detected during the testing of the product Assay kit for human Phosphatidylinositol 3 kinases 2a ...

http://phosphatidylinositol.com/products/8844-bluegen-elisas/9220-assay-kit-for-human-phosphatidylinositol-3-kinases-2a-elisa

Possible Involvement of Phosphatidylinositol-3 kinase and endothelial nitric oxide synthase' in experimental obesity ... Possible Involvement of Phosphatidylinositol-3 kinase and endothelial nitric oxide synthase' in experimental obesity ... This study was designed to investigate the possible role of Phosphatidylinositol-3 kinase (PI3K) and endothelial nitric oxide ... Phosphatidylinositol 3-Kinase, (SNP ): Sodium Nitroprusside, (VED): Vascular Endothelium Dysfunction. ...

https://imsear.searo.who.int/handle/123456789/151652

Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent update on inhibitor design and clinical trials (2016-2020). Expert ... Phosphatidylinositol 3-kinase (PI3K) inhibitors : a recent update on inhibitor design and clinical trials (2016-2020). In: ... Sabbah, D. A., Hajjo, R., Bardaweel, S. K., & Zhong, H. A. (2021). Phosphatidylinositol 3-kinase (PI3K) inhibitors: a recent ... Phosphatidylinositol 3-kinase (PI3K) inhibitors : a recent update on inhibitor design and clinical trials (2016-2020). / Sabbah ...

https://experts.nebraska.edu/en/publications/phosphatidylinositol-3-kinase-pi3k-inhibitors-a-recent-update-on-

Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer. 2003 Mar;3(3):155-68. doi: 10.1038/ ... human phosphatidylinositol 3-kinase homolog. *serine-protein kinase ATM. *TEL1. *TELO1. Additional Information & Resources. ... 2007 Jun;83(3):231-7. doi: 10.1016/j.radonc.2007.04.032. Epub 2007 May 23. Citation on PubMed ... DNA Repair (Amst). 2004 Aug-Sep;3(8-9):889-900. doi: 10.1016/j.dnarep.2004.03.029. Citation on PubMed ...

https://medlineplus.gov/genetics/gene/atm/

... protein kinase B; PTEN, phosphatase and tensin homolog; PIP2, phosphatidylinositol-4,5-bisphosphate; PIP3, phosphatidylinositol ... B-cell receptor signaling activates PI3K-mediated activation of the kinase AKT, which activates many downstream signaling ... 5-trisphosphate; IKK, IkB kinase; mTOR, mammalian target of rapamycin; FoxO, Forkhead box transcription factors; GSK3b, ... Grade 3-4 neutropenia and thrombocytopenia has been reported in only 20% and 10-25% of the patients, respectively. [126, 127] ...

http://emedicine.medscape.com/article/202969-treatment

The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after ... BACKGROUND: The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival ... NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and ... NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and ...

https://www.oncology.ox.ac.uk/publications/320452?d5e95f3c-7261-11ed-856e-061b866677b4

Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K ... Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K ... Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K ... Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K ...

https://ohsu.pure.elsevier.com/en/publications/t-cell-activation-dependent-association-between-the-p85-subunit-o-2

PI3K involvement was also shown by phosphorylation of the downstream effector protein kinase B. Spontaneous IL-10 production by ... inhibitors of phosphatidylinositol 3-kinase (PI3K), or of rapamycin, an inhibitor of p70 S6-kinase (p70S6K). Spontaneous IL-10 ... PI3K involvement was also shown by phosphorylation of the downstream effector protein kinase B. Spontaneous IL-10 production by ... Cytokine-stimulated T cells induce macrophage IL-10 production dependent on phosphatidylinositol 3-kinase and p70S6K: ...

https://www.immunology.ox.ac.uk/publications/224146

Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma. J Clin Oncol. 2017 Dec 10. ... Grade 3 disease is subdivided into grade 3A, in which centrocytes are present, [6] and grade 3B, in which folllicles composed ... WHO classification further classifies grade 3 into grades 3A and 3B. [6] Grade 3A has centrocytes present whereas grade 3B has ... 51] In this study, The progression-free survival at 3 years was 80% in the obinutuzumab-containing arm versus 73.3% in the ...

https://www.medscape.com/answers/203268-163288/what-is-the-role-of-bone-marrow-aspiration-in-the-diagnosis-of-follicular-lymphoma

Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream ... Fayard, Elisabeth, Moncayo, Gerald, Hemmings, Brian Arthur and Hollaender, Georg A (2010) Phosphatidylinositol 3-Kinase ... Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide-dependent protein kinase ( ... PDK1)-protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight ...

https://oak.novartis.com/3756/

Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream ... Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide-dependent protein kinase ( ... PDK1)-protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight ... Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-akt, Pyruvate Dehydrogenase (Acetyl-Transferring) Kinase, Signal ...

https://www.stemcells.ox.ac.uk/publications/309051

Phosphatidylinositol 3-kinase/Akt signaling enhances nuclear localization and transcriptional activity of BRCA1.. ... Phosphatidylinositol 3-kinase/Akt signaling enhances nuclear localization and transcriptional activity of BRCA1.. ...

https://www.meharryresearch.org/nlm-publication/phosphatidylinositol-3-kinase-akt-signaling-enhances-nuclear-localization-and-transcriptional-activity-of-brca1/

... cystathionine β-synthase and 3-mercaptosulfotransferase - can protect against cardiovascular pathologies, including arrhythmias ... Ca2+/calmodulin-dependent protein kinase II (CaMKII), a ubiquitous and abundant serine-threonine kinase, has emerged as an ... These effects were concentration-dependent and mediated via phosphatidylinositol 3-kinase (PI3K)-AKT1 signalling. The ... Protein kinase G Iα oxidation paradoxically underlies blood pressure lowering by the reductant hydrogen sulfide. Hypertension ...

https://www.nature.com/articles/s41569-022-00741-6?error=cookies_not_supported&code=271f9730-5002-4035-84bb-2aed32df8bd9

Eves EM, Xiong W, Bellacosa A, Kennedy SG, Tsichlis PN, Rosner MR, Hay N. Akt, a target of phosphatidylinositol 3-kinase, ... Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line.. ...

https://profiles.uchicago.edu/profiles/display/938019

It is reported that THC acute administration increases the phosphorylation of Akt in mouse hippocampus, striatum, and cerebellum, and activation of the PI3K/Akt/GSK‐3 signaling pathway may be related to the in vivo neuroprotective properties attributed to cannabinoids. (semanticscholar.org)
The phosphatidylinositol-3-kinase (PI3K) signaling pathway is an integral part of the BCR signaling machinery and its activity is indispensable for B-cell survival. (haematologica.org)
Investigation of phosphatidylinositol-3-kinase (PI3K). (ubc.ca)
Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase known to be a promising therapeutic target for cancer. (lifechemicals.com)
PI3K catalyzes phosphorylation of phosphatidyl-inositide in position 3 of the inositol ring, producing important lipid second messengers. (lifechemicals.com)
The products of PI3K activity recruit PDK1 and Akt Ser/Thr kinases to the plasma membrane where they are activated, transducing a potent proliferative and anti-apoptotic signal to the cell. (lifechemicals.com)
Dysregulation of this signaling pathway (PI3K/PDK1/Akt (also known as protein kinase B) has been found in a variety of cancer cells. (lifechemicals.com)
PI3K is a major signaling hub downstream of human epidermal growth factor receptor (HER)2 and other receptor tyrosine kinases. (biomedcentral.com)
PI3K activates AKT, serum/glucocorticoid regulated kinase (SGK), phosphoinositide-dependent kinase 1 (PDK1), mammalian target of rapamycin (mTOR), and several other molecules involved in cell cycle progression and survival. (biomedcentral.com)
PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate (PIP 2 ) to produce phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ). (biomedcentral.com)
Class IA PI3K isoforms are heterodimeric lipid kinases that contain a p110 catalytic subunit and a p85 regulatory subunit. (biomedcentral.com)
The phosphatidylinositol 3-kinase (PI3K) pathway regulates various cellular processes, including cellular proliferation and intracellular trafficking, and may affect prostate carcinogenesis. (ox.ac.uk)
This study was designed to investigate the possible role of Phosphatidylinositol-3 kinase (PI3K) and endothelial nitric oxide synthase (eNOS) in obesity-induced vascular endothelium dysfunction. (who.int)
Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway plays a central role in regulating cell growth and proliferation and thus has been considered as effective anticancer drug targets. (nebraska.edu)
BACKGROUND: The phosphatidylinositol 3-kinase (PI3K)/Akt pathway is activated in tumor cells and promotes tumor cell survival after radiation-induced DNA damage. (ox.ac.uk)
Elutriated monocytes were differentiated to macrophages by macrophage-colony-stimulating factor (M-CSF) and co-cultured with fixed T cells chronically stimulated in a cytokine cocktail of IL-2/IL-6/tumour necrosis factor (TNF)-alpha in the presence or absence of wortmannin and LY294002, inhibitors of phosphatidylinositol 3-kinase (PI3K), or of rapamycin, an inhibitor of p70 S6-kinase (p70S6K). (ox.ac.uk)
PI3K involvement was also shown by phosphorylation of the downstream effector protein kinase B. Spontaneous IL-10 production by RA-SMCs was also inhibited by LY294002 and depletion of the nonadherent (T-cell-enriched) fraction of the cell population. (ox.ac.uk)
Here, we discuss experimental evidence that argues for a critical role of the PI3K-phosphoinositide-dependent protein kinase (PDK1)-protein kinase B (PKB) signaling pathway in the development of both normal and malignant thymocytes, and we highlight molecules that can potentially be targeted therapeutically. (novartis.com)
These activating mutations improve the lipid kinase activity to an even greater than that of wild-type gene aren't the just deregulations from the PI3K pathway defined. (gasyblog.com)
Only PI3K inhibitor, but not kinase inhibitors for MEK, ERK1/2, p38 MAPK, JNK, protein kinase C, and protein kinase A, completely abolished this tumor cell contact-associated protection and in parallel restored Fas-induced Bcl-x L cleavage as well as decreasing the phosphorylation of Bad at serine 136. (aai.org)
Background: Platelet activation by collagen depends on signals transduced by the glycoprotein (GP)VI-Fc receptor (FcR)-chain collagen receptor complex, which involves recruitment of phosphatidylinositol 3-kinase (PI3K) to phosphorylated tyrosines in the linker for activation of T cells (LAT). (reading.ac.uk)
For instance, the kinase termed PI3K blocks the orderly process of cell death, called apoptosis. (dana-farber.org)
Background Combined inhibition of phosphatidylinositol 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) complexes may be an efficient treatment for acute leukemia. (researchsquare.com)
The phosphatidylinositol 3-kinase (PI3K) / Akt / mammalian target of rapamycin (mTOR) signaling axis plays an important physiologic role in protein synthesis, gene transcription, cell growth and apoptosis. (researchsquare.com)
In acute leukemias PI3K/Akt signaling activity was demonstrated to be correlated with an inferior prognosis via contribution to proliferation, survival and drug resistance in acute myeloid leukemia 3,10-12 , in T-cell acute lymphoblastic leukemia (T-ALL) 13 and B-cell precursor acute lymphoblastic leukemia (BCP-ALL). (researchsquare.com)
14,15,16 Herein in Philadelphia chromosome positive (Ph+) BCP-ALL PI3K signaling has been shown to be involved in mutation-independent resistance to ABL-directed tyrosine kinase inhibitors 14 and recent preclinical data also suggest a role in Philadelphia chromosome negative (Ph-) BCP-ALL. (researchsquare.com)
While mutations of the PI3KCA gene are rare in leukemia, events upstream of PI3K are commonly implicated in causing aberrant activation of this pathway, e.g. activating mutations of the receptor tyrosine kinases (RTKs), Fms-like tyrosine kinase 3 ( FLT3 ) and KIT receptor tyrosine kinase, BCR-ABL1 fusion gene, or activating mutations in NRas and KRas . (researchsquare.com)

Nuclear ARE activation and rGSTA2 mRNA increase were both completely inhibited by wortmannin or LY294002, the phosphatidylinositol 3-kinase (PI3-kinase) inhibitors. (aspetjournals.org)
NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity. (ox.ac.uk)
Furthermore, wortmannin and LY294002, two PI-3 kinase inhibitors, markedly decreased AP-1 activity induced by insulin, TPA, or TPA and insulin and inhibited JB6 promotion-sensitive cell transformation induced by TPA or TPA and insulin. (umn.edu)
He has extended his work to stimulate the discovery of clinically useful inhibitors of oncogenic kinases. (dana-farber.org)
This class of drugs, called kinase inhibitors, offers extraordinary hope for the future of cancer care. (dana-farber.org)
It is indicated for adults with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) who were previously treated with ≥2 tyrosine kinase inhibitors (TKIs). (medscape.com)

A phosphatidylinositol 3-kinase-independent insulin signaling pathway to N-WASP/Arp2/3/F-actin required for GLUT4 glucose transporter recycling. (umassmed.edu)
Exposure to asphalt fumes activates activator protein-1 through the phosphatidylinositol 3-Kinase/Akt signaling pathway in mouse epidermal cells. (cdc.gov)

Here, we demonstrate that in Jurkat T cells, pp36/38 associates with the p85 subunit of phosphatidylinositol 3-kinase (PI-3-K p85) in an activation-dependent manner. (elsevier.com)
Although the p85(IS) domain conferred a strong interaction with the p110 catalytic subunit, this region was not sufficient to impart phosphotyrosine peptide stimulation of PI 3-kinase activity. (elsevier.com)
In contrast, coexpression of the p110 subunit with full-length p85 or with constructs containing the IS sequences flanked by both SH2 domains of p85 [p85(n/cSH2)] or either of the individual SH2 domains [p85(nSH2+IS) or p85(IS+cSH2)] resulted in PI 3-kinase activity that was activated by a phosphotyrosine peptide. (elsevier.com)

Currently, little is known about whether phosphatidylinositol-3 (PI-3) kinase plays any role in phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced signal transduction. (umn.edu)
Activation of the Janus kinase/STAT (signal transducer and activator of transcription) signal transduction pathway by interleukin-6-type cytokines promotes osteoblast differentiation. (uams.edu)

It is shown that lipid rafts control CB1R, but not CB2R, and endocannabinoid transport in immune and neuronal cells, and that receptor activation triggers similar [35S]guanosine-5′-O-(3-thiotriphosphate) binding in MCD-treated and control cells, similar adenylate cyclase and MAPK activity, and similar MAPK-dependent protection against apoptosis. (semanticscholar.org)
Together, these findings strongly suggest that oral administration of probiotics may attenuate cardiomyocyte apoptosis by activation of the phosphatidylinositol‑3 kinase/AKT survival‑signalling pathway in obese rats. (spandidos-publications.com)
Fas ligand and death receptor protein levels, as well as activities of caspase-8 and caspase-3, were significantly upregulated in hearts from obese rats, suggesting the involvement of Fas receptor-dependent apoptosis in obesity-associated heart disease ( 13 ). (spandidos-publications.com)
Akt, a target of phosphatidylinositol 3-kinase, inhibits apoptosis in a differentiating neuronal cell line. (uchicago.edu)
This effect was specific for the inhibition of PI-3K because inhibition of other signaling pathways such as extracellular signaling-regulated kinase (ERK), p38, or p70S6 kinase did not affect spontaneous apoptosis. (ashpublications.org)
Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. (idrblab.net)
Bellido T, Huening M, Raval-Pandya M, Manolagas SC, Christakos S. Calbindin-D28k is expressed in osteoblastic cells and suppresses their apoptosis by inhibiting caspase-3 activity. (uams.edu)
Almeida M, Han L, Bellido T, Manolagas SC, Kousteni S. Wnt proteins prevent apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts by beta-catenin-dependent and -independent signaling cascades involving Src/ERK and phosphatidylinositol 3-kinase/AKT. (uams.edu)

Phorbol esters, which activate isoforms of protein kinase C, are general activators of the transcription factor activated protein 1 (AP-1). (umn.edu)
We demonstrated that protein kinase B/Akt is expressed in all tested CLL samples but no activation of Akt was detected. (ashpublications.org)
In contrast, we observed a constitutive activation of protein kinase Cδ (PKCδ) in freshly isolated B-CLL cells. (ashpublications.org)
In this study, we found ten point mutations in the gene encoding homeodomain-interacting protein kinase 4 (HIPK4) in patients with NOA, and using in vitro studies, we determined a premature termination point mutation (p. (jbc.org)
Activation of protein kinase C in contrast suppressed phosphorylation of ezrin and moesin. (uni-konstanz.de)

Phosphatidylinositol-3-Kinase/Akt regulates bleomycin-induced fibroblast proliferation and collagen production. (cdc.gov)
Caveolin-1 interacts with and negatively regulates the EGFR, PDGFR, and Neu tyrosine kinases, Ha-Ras, c-Src, and phosphatidylinositol 3-kinase. (sputnic-group.ru)
In mice, the DNA damage-regulated phosphatidylinositol-3-kinase-like kinase (PIKK) ATM regulates all of these processes. (figshare.com)

Particularly, triggered PI3Ks catalyze the phosphorylation of phosphatidylinositol-4,5 bisphosphate (PIP2) to create the next messenger phosphatidylinositol-3,4,5 trisphosphate (PIP3). (gasyblog.com)
Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. (idrblab.net)
We further show that endogenous ezrin and moesin are phosphorylated and that activities of PI-3 kinase, Rho and Rac, but not of Rho-kinase, are required for this C-terminal phosphorylation. (uni-konstanz.de)

Asciminib is a tyrosine kinase inhibitor that binds to ABL myristoyl pockets, thereby inhibiting ABL1 kinase activity of the BCR-ABL1 fusion protein. (medscape.com)

Inhibition of p38 MAP kinase by SB203580 prevented the ARE-mediated rGSTA2 induction. (aspetjournals.org)
Importantly, the upregulation of nicotine-increased surface molecules upregulation was significantly abrogated by the inhibition of Akt kinase. (hindawi.com)

phosphatidylinositol 4-kinase;Phosphoinositide 3-kinase. (ntu.edu.sg)

Among the key pathways are those controlling cell proliferation , which coordinate a response to the cellular environment, with the mTOR kinase as a critical node. (axonmedchem.com)

RTK, receptor tyrosine kinase. (biomedcentral.com)
EGFR can be a transmembrane receptor tyrosine kinase that is one of the HER category of receptors. (colinsbraincancer.com)
PAPbeta, a protein that binds to and is phosphorylated by the non-receptor tyrosine kinase PYK2, contains several modular signaling domains including a pleckstrin homology domain, an SH3 domain, ankyrin repeats and an ARF-GAP domain. (embl.de)

Subclass IA users are triggered by ligand binding of receptor tyrosine kinases (RTK), whereas Subclass IB users are triggered by G protein-coupled receptors. (gasyblog.com)
Dr. Roberts has played a seminal role in discovering the conceptual fabric of signaling downstream from tyrosine kinases. (dana-farber.org)
We supply the company with the reagents necessary to test the effect of drugs on the action of tyrosine kinases. (dana-farber.org)

Regulation of the Tumor-Suppressor Function of the Class III Phosphatidylinositol 3-Kinase Complex by Ubiquitin and SUMO. (ruhr-uni-bochum.de)
Every tumor is unique, with its own pattern of activated kinases. (dana-farber.org)
Because there are more than 600 different kinases in a given tumor, it is important to find which ones are activated so that we know which ones to inhibit. (dana-farber.org)

In turn, PIP 3 recruits to the plasma membrane several pleckstrin homology (PH) domain-containing proteins, such as PDK1 and AKT, which, upon activation, drive cell cycle progression and survival. (biomedcentral.com)
In vitro binding experiments with glutathione S-transferase fusion proteins of PI-3-K p85 demonstrated that the SH2 domains, but not the SH3 domain, mediated binding to pp36/38. (elsevier.com)
These results strongly suggest the role of pp36/38 in recruiting PI- 3-K to the cell membrane and further support the idea that pp36/38 is a multifunctional docking protein for SH2 domain-containing signaling proteins in T cells. (elsevier.com)
The era of PIP3 activates downstream signaling effector proteins, like the serine/threonine kinase AKT. (gasyblog.com)
[2] [3] Many membrane receptors include transmembrane proteins . (ipfs.io)

most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. (idrblab.net)

Although previous studies revealed that ex vivo nicotine stimulation increases antigen internalization and promotes imDCs' cross-presentation [ 3 - 6 ], the exact effect of endosomal translocation of internalized antigen in nicotine-increased cross-presentation is still uncertain, nevertheless the effect of nicotine on the transporting internalized antigen to cytoplasm. (hindawi.com)

The activation of p38 MAP kinase, however, failed to be inhibited by wortmannin or LY294002, showing that PI3-kinase is not involved in the activation of p38 MAP kinase. (aspetjournals.org)

gene, mutation, breasts malignancy Phosphatidylinositol-3 kinases TPCA-1 (PI3Ks) certainly are a well-characterized category of lipid kinases which were originally recognized by their capability to phosphorylate the 3-hydroxy band of inositol phospholipids. (gasyblog.com)
An overactive kinase can lead to an overactive gene and, ultimately, to cancer. (dana-farber.org)
Three strains of Elizabethkingia -like, gram-negative bacilli sharing similar phenotypic characteristics were isolated from the 3 patients, but confident identification results were not obtained by matrix-assisted laser desorption ionization/time-of-flight (MALDI-TOF) mass spectrometry and 16S rRNA gene sequencing. (cdc.gov)

DCMPT64 expressed a high level of immunosuppressive molecules PD-L1, TIM-3, nitric oxide (NO), arginase 1, IDO-1, IL-10 and TGF-ß, but inhibited the production of pro-inflammatory cytokines TNF-α, IL-6 and IL-12. (bvsalud.org)

The p38 mitogen-activated protein (MAP) kinase was activated at 0.5 to 3 h after SAAD, followed by sustained diminished activation up to 12 h. (aspetjournals.org)
Most importantly, constitutive overexpression of the dominant negative PI-3 kinase P85 mutants completely blocked insulin- or TPA-induced AP-1 trans-activation and TPA-induced cell transformation. (umn.edu)
All evidence from present studies suggests that PI-3 kinase acts as a mediator in TPA-induced AP-1 activation and transformation in JB6 cells. (umn.edu)
This was indicated by less plasma membrane alteration, an amelioration of the loss of mitochondria membrane potential, a decrease in caspase-8 and caspase-3 activation, a decrease in DNA fragmentation factor-45/35 cleavage, and a reduction in the breakage of DNA when compared with Jurkat cells cultured alone. (aai.org)
Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. (idrblab.net)
Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. (idrblab.net)
Constitutive activation of phosphatidylinositol-3 kinase (PI 3-kinase), Rac, Rho and Rho kinase are essential for these processes. (uni-konstanz.de)

We demonstrate here that TPA not only has markedly synergistic effects on insulin-induced PI-3 kinase activity, but it also can induce PI-3 kinase activity and the PI-3 phosphates by itself. (umn.edu)
We also found that insulin, a PI-3 kinase activator, enhanced TPA-induced AP-1 transactivation and transformation in JB6 promotion-sensitive cells. (umn.edu)

Domains of interaction between the p85 and p110 subunits of phosphatidylinositol 3-kinase (PI 3-kinase) were studied with the yeast two- hybrid expression system. (elsevier.com)
Synthetic peptide within Human PI3 Kinase p110 beta aa 400-500. (abcam.com)

Various preclinical and clinical studies have shown that H 2 S and its synthesizing enzymes - cystathionine γ-lyase, cystathionine β-synthase and 3-mercaptosulfotransferase - can protect against cardiovascular pathologies, including arrhythmias, atherosclerosis, heart failure, myocardial infarction and ischaemia-reperfusion injury. (nature.com)
This process is facilitated by a class of enzymes called kinases, which help activate specific genes in the long strands of DNA in a cell's nucleus. (dana-farber.org)

Phosphatidylinositol 3-kinases (PI3Ks) play a critical role in thymocyte development, although not all of their downstream mediators have yet been identified. (novartis.com)
PI3Ks are split into three different classes (I-III) predicated on structural homology and substrate[3],[4]. (gasyblog.com)

Caveolin-1 links integrin subunits to the tyrosine kinase FYN, an initiating step in coupling integrins to the Ras-ERK pathway. (sputnic-group.ru)

In previous studies, we have demonstrated that ex vivo nicotine stimulation has stimulatory effects on murine bone marrow-derived semimature DCs (imDCs), which reveal efficient upregulation of surface molecules through α 7 nicotinic acetylcholine receptor (nAchR) [ 3 - 6 ]. (hindawi.com)

Predicted to be part of phosphatidylinositol 3-kinase complex. (jax.org)
XIII" YMR047C 3 13 3 YMR047C "Nuclear pore complex protein that is member of GLFG repeat-containing family of nucleoporins and is,XIII" YMR049C 3 13 4 YMR049C "Ymr049cp,XIII" YMR051C 3 13 5 YMR051C "TyA Gag protein. (davidson.edu)

Data showed that PI3-kinase plays an essential role in the ARE-mediated rGSTA2 induction by oxidative stress after SAAD, which activates the p38 MAP kinase and leads to rGSTA2 induction. (aspetjournals.org)

Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer. (ox.ac.uk)
One is how particular kinases are involved in cancer. (dana-farber.org)

Filter binding assays demonstrated that association between pp36/38 and PI-3-K p85 SH2 domains was due to direct binding. (elsevier.com)

Negative regulation of this pathway is conferred by PTEN and INPP4B, which dephosphorylate PIP 3 and PIP 2 , respectively. (biomedcentral.com)

Phosphatidylinositol 3-kinase/Akt signaling enhances nuclear localization and transcriptional activity of BRCA1. (meharryresearch.org)
We are also exploring new ways to measure kinase activity in tumors. (dana-farber.org)
this increases SRC kinase activity. (idrblab.net)
Often, this is tyrosine kinase activity. (ipfs.io)

Cytokine-stimulated T cells induce macrophage IL-10 production dependent on phosphatidylinositol 3-kinase and p70S6K: implications for rheumatoid arthritis. (ox.ac.uk)

It is also a negative regulator of the Ras-p42/44 mitogen-activated kinase cascade. (sputnic-group.ru)

Anatomy19

Organisms8

Diseases1

Chemicals and Drugs174

Analytical, Diagnostic and Therapeutic Techniques and Equipment12

Phenomena and Processes37

Information Science3

Vac1p coordinates Rab and phosphatidylinositol 3-kinase signaling in Vps45p-dependent vesicle docking/fusion at the endosome. (1/13288)

Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis. (2/13288)

Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. (3/13288)

Role of alphavbeta3 integrin in the activation of vascular endothelial growth factor receptor-2. (4/13288)

The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase. (5/13288)

Signals from the Ras, Rac, and Rho GTPases converge on the Pak protein kinase in Rat-1 fibroblasts. (6/13288)

Salmonella typhimurium and lipopolysaccharide stimulate extracellularly regulated kinase activation in macrophages by a mechanism involving phosphatidylinositol 3-kinase and phospholipase D as novel intermediates. (7/13288)

Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Involvement of Jak2 in the stimulation of phosphatidylinositol 3-kinase. (8/13288)

Phosphatidylinositol 3-Kinases

Phosphatidylinositol Phosphates

1-Phosphatidylinositol 4-Kinase

Phosphatidylinositol 4,5-Diphosphate

Phosphatidylinositols

Protein-Serine-Threonine Kinases

Phosphotransferases (Alcohol Group Acceptor)

MAP Kinase Signaling System

Chromones

Androstadienes

Phosphatidylinositol 3-Kinase

Protein Kinases

Morpholines

Proto-Oncogene Proteins c-akt

Signal Transduction

Protein Kinase Inhibitors

Phosphorylation

Calcium-Calmodulin-Dependent Protein Kinases

src-Family Kinases

Protein Kinase C

Enzyme Activation

Proto-Oncogene Proteins

Mitogen-Activated Protein Kinase 1

p38 Mitogen-Activated Protein Kinases

Protein-Tyrosine Kinases

Enzyme Inhibitors

Cyclic AMP-Dependent Protein Kinases

Ribosomal Protein S6 Kinases

Mitogen-Activated Protein Kinase Kinases

Mitogen-Activated Protein Kinase 3

Type C Phospholipases

JNK Mitogen-Activated Protein Kinases

Cell Line

Mitogen-Activated Protein Kinases

p21-Activated Kinases

Phosphoproteins

Isoenzymes

Phosphoric Monoester Hydrolases

CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase

Kinetics

Inositol

Molecular Sequence Data

Protein Binding

Transfection

Phosphatidylinositol Diacylglycerol-Lyase

Cells, Cultured

Tyrosine

Extracellular Signal-Regulated MAP Kinases

MAP Kinase Kinase Kinases

Glycogen Synthase Kinase 3

Cell Membrane

Cyclin-Dependent Kinases

MAP Kinase Kinase 1

Mutation

Receptor Protein-Tyrosine Kinases

Amino Acid Sequence

Phospholipids

Creatine Kinase

CDC2 Protein Kinase

Casein Kinase II

Casein Kinases

Blotting, Western

Calcium

eIF-2 Kinase

TOR Serine-Threonine Kinases

Intracellular Signaling Peptides and Proteins

Apoptosis

Phosphotransferases

3T3 Cells

Pyruvate Kinase

Protein Structure, Tertiary

Insulin Receptor Substrate Proteins

Diacylglycerol Kinase

Recombinant Fusion Proteins

Recombinant Proteins

MAP Kinase Kinase 4

Cell Line, Tumor

Insulin

Class Ib Phosphatidylinositol 3-Kinase

Thymidine Kinase