An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.
A subclass of receptor-like protein tryosine phosphatases that contain multiple extracellular immunoglobulin G-like domains and fibronectin type III-like domains. An additional memprin-A5-mu domain is found on some members of this subclass.
A subtype of non-receptor protein tyrosine phosphatases that contain two SRC HOMOLOGY DOMAINS. Mutations in the gene for protein tyrosine phosphatase, non-receptor type 11 are associated with NOONAN SYNDROME.
A subtype of non-receptor protein tyrosine phosphatase that is closely-related to PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1. Alternative splicing of the mRNA for this phosphatase results in the production at two gene products, one of which includes a C-terminal nuclear localization domain that may be involved in the transport of the protein to the CELL NUCLEUS. Although initially referred to as T-cell protein tyrosine phosphatase the expression of this subtype occurs widely.
A Src-homology domain-containing protein tyrosine phosphatase found in the CYTOSOL of hematopoietic cells. It plays a role in signal transduction by dephosphorylating signaling proteins that are activated or inactivated by PROTEIN-TYROSINE KINASES.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.
A subcategory of protein tyrosine phosphatases that occur in the CYTOPLASM. Many of the proteins in this category play a role in intracellular signal transduction.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular fibronectin III-like domain along with a carbonic anhydrase-like domain.
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.
Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.
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.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of a N-terminal catalytic domain and a large C-terminal domain that is enriched in PROLINE, GLUTAMIC ACID, SERINE, and THREONINE residues (PEST sequences). The phosphatase subtype is ubiquitously expressed and implicated in the regulation of a variety of biological processes such as CELL MOVEMENT; CYTOKINESIS; focal adhesion disassembly; and LYMPHOCYTE ACTIVATION.
A subcategory of protein tyrosine phosphatases that are bound to the cell membrane. They contain cytoplasmic tyrosine phosphatase domains and extracellular protein domains that may play a role in cell-cell interactions by interacting with EXTRACELLULAR MATRIX components. They are considered receptor-like proteins in that they appear to lack specific ligands.
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.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
A subcategory of protein tyrosine phosphatases that contain SH2 type SRC HOMOLOGY DOMAINS. Many of the proteins in this class are recruited to specific cellular targets such as a cell surface receptor complexes via their SH2 domain.
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.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing five different PDZ domains, and a carboxyl-terminal phosphatase domain. In addition to playing a role as a regulator of the FAS RECEPTOR activity this subtype interacts via its PDZ and FERM domains with a variety of INTRACELLULAR SIGNALING PROTEINS and CYTOSKELETAL PROTEINS.
A subclass of receptor-like protein tryosine phosphatases that contain a short extracellular domain, a cytosolic kinase-interaction domain, and single protein tyrosine kinase domain.
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.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
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.
Established cell cultures that have the potential to propagate indefinitely.
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 subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an N-terminal catalytic domain and a C-terminal PROLINE-rich domain. The phosphatase subtype is predominantly expressed in LYMPHOCYTES and plays a key role in the inhibition of downstream T-LYMPHOCYTE activation. Polymorphisms in the gene that encodes this phosphatase subtype are associated with a variety of AUTOIMMUNE DISEASES.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.
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.
Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing one or more PDZ domains, and a carboxyl-terminal phosphatase domain. Expression of this phosphatase subtype has been observed in BONE MARROW; fetal LIVER; LYMPH NODES; and T LYMPHOCYTES.
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.
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.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A eukayrotic protein serine-threonine phosphatase subtype that dephosphorylates a wide variety of cellular proteins. The enzyme is comprised of a catalytic subunit and regulatory subunit. Several isoforms of the protein phosphatase catalytic subunit exist due to the presence of multiple genes and the alternative splicing of their mRNAs. A large number of proteins have been shown to act as regulatory subunits for this enzyme. Many of the regulatory subunits have additional cellular functions.
A phosphoprotein phosphatase subtype that is comprised of a catalytic subunit and two different regulatory subunits. At least two genes encode isoforms of the protein phosphatase catalytic subunit, while several isoforms of regulatory subunits exist due to the presence of multiple genes and the alternative splicing of their mRNAs. Protein phosphatase 2 acts on a broad variety of cellular proteins and may play a role as a regulator of intracellular signaling processes.
Agents that inhibit PROTEIN KINASES.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
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.
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.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
The rate dynamics in chemical or physical systems.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Proteins prepared by recombinant DNA technology.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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.
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)
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 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.
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.
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.
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.
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 non-receptor, PROLINE-rich protein-tyrosine kinases.
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 protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
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.
LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.
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.
Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
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).
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 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
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.
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.
An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC
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 conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
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 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.
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing one or more PDZ domains, and a carboxyl-terminal phosphatase domain. The subtype was originally identified in a cell line derived from MEGAKARYOCYTES.
Physiologically inactive substances that can be converted to active enzymes.
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 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
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.
Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A cell line derived from cultured tumor cells.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
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.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
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.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
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).
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
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.
Adherence of cells to surfaces or to other cells.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
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 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.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
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.
Members of the src-family tyrosine kinases that are activated during the transition from G2 PHASE to M PHASE of the CELL CYCLE. It is highly homologous to PROTO-ONCOGENE PROTEIN PP60(C-SRC).
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 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.
Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.
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.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Elements of limited time intervals, contributing to particular results or situations.
Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.
Transport proteins that carry specific substances in the blood or across cell membranes.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
A sub-class of protein tyrosine phosphatases that contain an additional phosphatase activity which cleaves phosphate ester bonds on SERINE or THREONINE residues that are located on the same protein.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
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.
The sum of the weight of all the atoms in a molecule.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
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.
Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20.
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 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.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
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.
Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
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.
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 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.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
A tyrosine-specific protein kinase encoded by the v-src oncogene of ROUS SARCOMA VIRUS. The transforming activity of pp60(v-src) depends on both the lack of a critical carboxy-terminal tyrosine phosphorylation site at position 527, and the attachment of pp60(v-src) to the plasma membrane which is accomplished by myristylation of its N-terminal glycine.
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A specific inhibitor of phosphoserine/threonine protein phosphatase 1 and 2a. It is also a potent tumor promoter. (Thromb Res 1992;67(4):345-54 & Cancer Res 1993;53(2):239-41)
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
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.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
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.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
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.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Inorganic or organic compounds that contain arsenic.
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).
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
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 family of signaling adaptor proteins that contain SRC HOMOLOGY DOMAINS. Many members of this family are involved in transmitting signals from CELL SURFACE RECEPTORS to MITOGEN-ACTIVATED PROTEIN KINASES.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
The phosphoric acid ester of serine.
Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the PTPRF gene. The protein encoded by ... functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and ... "The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has ... "Entrez Gene: PTPRF protein tyrosine phosphatase, receptor type, F". Bonvini P, An WG, Rosolen A, Nguyen P, Trepel J, Garcia de ...
"Entrez Gene: PTPRB protein tyrosine phosphatase, receptor type, B". Fachinger G, Deutsch U, Risau W (Oct 1999). "Functional ... have shown that tyrosine phosphorylation of VE-PTP via Pyk2 kinase downstream of STIM1-induced calcium entry mediates ... Receptor-type tyrosine-protein phosphatase beta or VE-PTP is an enzyme specifically expressed in endothelial cells that in ... Gaits F, Li RY, Ragab A, Ragab-Thomas JM, Chap H (1995). "Increase in receptor-like protein tyrosine phosphatase activity and ...
CD45 - a transmembrane protein whose intracellular tail functions as a tyrosine phosphatase that activates Src family kinases ... "Selection of functional T cell receptor mutants from a yeast surface-display library". Proceedings of the National Academy of ... or any other cell type (MHC class I) [11] High on-rate and off-rate is characteristic for TCR and peptide/MHC interaction at ... UMich Orientation of Proteins in Membranes protein/pdbid-2hac - Zeta-zeta dimer of T cell receptor ...
... a transmembrane tyrosine kinase-receptor, leading to secondary messenger activation of tyrosine kinase Src. Both of these ... Cathepsin K is the major protease involved in the degradation of type I collagen and other noncollagenous proteins. Mutations ... Cathepsin K transmigrates across the ruffled border by intercellular vesicles and is then released by the functional secretory ... This permits characterization of osteoclasts by their staining for high expression of tartrate resistant acid phosphatase (TRAP ...
... an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases". Mol. Cell. Biol. 10 (12): 6316- ... EPH receptor A2 (ephrin type-A receptor 2) is a protein that in humans is encoded by the EPHA2 gene. This gene belongs to the ... Kinch MS, Carles-Kinch K (2003). "Overexpression and functional alterations of the EphA2 tyrosine kinase in cancer". Clin. Exp ... "Regulation of the EphA2 kinase by the low molecular weight tyrosine phosphatase induces transformation". J. Biol. Chem. 277 (42 ...
Similarly, both dual-specificity MAP kinase phosphatases and MAP-specific tyrosine phosphatases bind to MAP kinases through the ... A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of protein kinase that is specific to the amino acids serine ... receptor tyrosine kinases, Ras or Raf proteins. Although no MKK1/2 or ERK1/2 inhibitors were developed for clinical use, kinase ... Mice that were genetically engineered to lack a functional JNK3 gene - the major isoform in brain - display enhanced ischemic ...
Mendrola JM, Shi F, Park JH, Lemmon MA (August 2013). "Receptor tyrosine kinases with intracellular pseudokinase domains". ... Protein Ser/Thr phosphatases were originally classified using biochemical assays as either, type 1 (PP1) or type 2 (PP2), and ... and that several enzymes have separate phosphorylation sites for activating or inhibiting functional regulation. CDK, for ... The protein Tyr phosphatase (PTP) super-family forms the second group, and the aspartate-based protein phosphatases the third. ...
Activation of the receptor tyrosine kinases generates a signaling cascade where the Ras GTPase proteins are activated to a GTP- ... Which forms functional intracellular tyrosine kinases. ErbB2 has no known binding ligand and absent of an active kinase domain ... while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor. ErbB protein ... Many breast tumors also have lower levels of PTEN, which is a lipid phosphatase that dephosphorylates phosphatidylinositol (3,4 ...
"Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Possible ... "Interaction of wild type and dominant-negative p55PIK regulatory subunit of phosphatidylinositol 3-kinase with insulin-like ... IRS-1 has a functional role in breast cancer progression and metastasis. Overexpression of PTEN in MCF-7 epithelial breast ... Tyrosine phosphorylation of IRS-1 by insulin receptor (IR) introduces multiple binding sites for proteins bearing SH2 homology ...
... the two lipid phosphatases SHIP1 and SHIP2 and the two protein tyrosine phosphatases(PTPs) SHP-1 and SHP-2. The ... the activating NK cell receptor NKp44 contains an ITIM, but this seems to be non-functional. Some of the important receptors ... In order to become phosphorylated, the inhibitory receptor has to be brought in close proximity to the kinase. This may be ... There are several isoforms of SHIP and the expression of these isoforms differs among different cell types.. In addition, ...
Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the PTPRC gene. ... "The human cytomegalovirus UL11 protein interacts with the receptor tyrosine phosphatase CD45, resulting in functional paralysis ... Koretzky GA, Kohmetscher M, Ross S (April 1993). "CD45-associated kinase activity requires lck but not T cell receptor ... "Entrez Gene: PTPRC protein tyrosine phosphatase, receptor type, C". Holmes N (February 2006). "CD45: all is not yet crystal ...
... while receptor protein tyrosine phosphatases (RPTP) (e.g. CD45, CD148) mediate the dephosphorylation of the same residues. SFK ... Non-catalytic tyrosine-phosphorylated receptors (NTRs), also called immunoreceptors or Src-family kinase-dependent receptors, ... The functional response of the leukocytes depends on the integration of the signals. Veillette A, Latour S, Davidson D (2002 ... At any given time, multiple NTR types can be engaged with their receptive ligands, inducing activatory, costimulatory as well ...
Protein tyrosine phosphatase, non-receptor type 22 (lymphoid), also known as PTPN22, is a protein that in humans is encoded by ... "Association of inhibitory tyrosine protein kinase p50csk with protein tyrosine phosphatase PEP in T cells and other hemopoietic ... "A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes". Nat. Genet. 36 (4): 337-8. doi: ... for association of protein-tyrosine phosphatase PEP with the Src homology 3 domain of inhibitory tyrosine protein kinase p50( ...
"Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase". The ... "The functional significance of Shc in insulin signaling as a substrate of the insulin receptor". Endocrine Journal. 47 (4): 373 ... "Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium ... Lck is a tyrosine kinase, which phosphorylates tyrosine residues of certain proteins involved in the intracellular signaling ...
JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the ... "Functional cooperation of the interleukin-2 receptor beta chain and Jak1 in phosphatidylinositol 3-kinase recruitment and ... "Molecular characterization of specific interactions between SHP-2 phosphatase and JAK tyrosine kinases". J. Biol. Chem. 272 (2 ... 1994). "Tyrosine kinase JAK1 is associated with the granulocyte-colony-stimulating factor receptor and both become tyrosine- ...
... receptor tyrosine kinases (RTKs), cytokine receptors (JAK/STATs), as well as modulation of various other "accessory" proteins ... to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs ... the bradykinin receptor B2 has been shown to interact directly with a protein tyrosine phosphatase. The presence of a tyrosine- ... receptor domain by protein kinases. Phosphorylation by cAMP-dependent protein kinasesEdit. Cyclic AMP-dependent protein kinases ...
2001). "Protein-tyrosine phosphatase D1, a potential regulator and effector for Tec family kinases". J. Biol. Chem. 275 (52): ... 2002). "Etk/Bmx as a Tumor Necrosis Factor Receptor Type 2-Specific Kinase: Role in Endothelial Cell Migration and Angiogenesis ... 2002). "Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx". J. Biol. Chem. 277 (11): 9351-7. doi: ... Cytoplasmic tyrosine-protein kinase BMX is an enzyme that in humans is encoded by the BMX gene. Tyrosine kinases are either ...
Smad target gene protein tyrosine phosphatase receptor type kappa is required for TGF-{beta} function". Molecular and Cellular ... adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated protein kinase ... "A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling". Nature Biotechnology. 21 ... Tiganis T (January 2002). "Protein tyrosine phosphatases: dephosphorylating the epidermal growth factor receptor". IUBMB Life. ...
Yoshida K, Kufe D (December 2001). "Negative regulation of the SHPTP1 protein tyrosine phosphatase by protein kinase C delta in ... Protein kinase C delta type (or PKC-δ) is an enzyme that in humans is encoded by the PRKCD gene. Protein kinase C (PKC) is a ... "Functional interaction between RAFT1/FRAP/mTOR and protein kinase cdelta in the regulation of cap-dependent initiation of ... "Insulin induces specific interaction between insulin receptor and protein kinase C delta in primary cultured skeletal muscle". ...
"Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl ... Cao C, Leng Y, Li C, Kufe D (April 2003). "Functional interaction between the c-Abl and Arg protein-tyrosine kinases in the ... "Direct interaction of nerve growth factor receptor, TrkA, with non-receptor tyrosine kinase, c-Abl, through the activation loop ... Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ...
"Physical and functional interactions between protein tyrosine phosphatase alpha, PI 3-kinase, and PKCdelta". Biochem. Biophys. ... "Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors". ... 1996). "Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal ... phosphatidylinositol 3-kinase beta, and protein kinase Cepsilon". J. Biol. Chem. 273 (48): 32016-22. doi:10.1074/jbc.273.48. ...
Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene. The protein encoded by ... Rosdahl JA, Mourton TL, Brady-Kalnay SM (2002). "Protein kinase C delta (PKCdelta) is required for protein tyrosine phosphatase ... Crystallographic studies demonstrated that the MAM and Ig domains are tightly associated into one functional entity. Additional ... Protein tyrosine phosphatases are protein enzymes that remove phosphate moieties from tyrosine residues on other proteins. ...
... receptor tyrosine kinases (RTKs), cytokine receptors (JAK/STATs), as well as modulation of various other "accessory" proteins ... to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type (Gαs ... October 2002). "A novel protein-protein interaction between a G protein-coupled receptor and the phosphatase SHP-2 is involved ... receptor domain by protein kinases. Cyclic AMP-dependent protein kinases (protein kinase A) are activated by the signal chain ...
They are cytosolic tyrosine kinases that are specifically associated with cytokine receptors. Since cytokine receptor proteins ... JAK3 is involved in signal transduction by receptors that employ the common gamma chain (γc) of the type I cytokine receptor ... However, Shc recruited tyrosine phosphatase SHP-2 and PTP-1B to Jak3 and thereby dephosphorylate Jak3. Thus the study not only ... Functional reconstitution of kinase activity by recombinant Jak3 using Jak3-wt or villin/gelsolin-wt as substrate showed that ...
"Regulation of AMP-activated protein kinase activity by G-protein coupled receptors: potential utility in treatment of diabetes ... 2011). "Protein kinases and phosphatases in the control of cell fate". Enzyme Res. 2011: 329098. doi:10.4061/2011/329098. PMC ... Phosphorylation and dephosphorylation can be used on all types of substrates, such as structural proteins, enzymes, membrane ... and tyrosine within specific target proteins is a fundamental part of the regulation of every physiologic process. ...
Receptor-type tyrosine-protein phosphatase PCP-2 (also known as PTP-pi, PTP lambda, hPTP-J, PTPRO and PTP psi), is an enzyme ... 2002). "Physical and functional interaction between receptor-like protein tyrosine phosphatase PCP-2 and beta-catenin". ... PCP-2 protein expression in these cell lines is increased by PMA stimulation. PCP-2 and the c-Kit tyrosine kinase receptor ... "Entrez Gene: PTPRU protein tyrosine phosphatase, receptor type, U". Crossland S, Smith PD, Crompton MR (1996). "Molecular ...
Receptor-type tyrosine-protein phosphatase T is an enzyme that in humans is encoded by the PTPRT gene. PTPRT is also known as ... 2010). "Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T". ... by tyrosine phosphorylation of the wedge domain of the first tyrosine phosphatase domain on tyrosine 912 by Fyn tyrosine kinase ... "Entrez Gene: PTPRT protein tyrosine phosphatase, receptor type, T". Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, ...
"Fyn kinase-directed activation of SH2 domain-containing protein-tyrosine phosphatase SHP-2 by Gi protein-coupled receptors in ... gamma subunit of the type 6 retinal cGMP phosphodiesterase functions to link c-Src and G-protein-coupled receptor kinase 2 in a ... "Functional importance of Shc tyrosine 317 on insulin signaling in Rat1 fibroblasts expressing insulin receptors". The Journal ... "Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein ...
Downstream effectors of NRG-1/ErbB, include cardiac-specific myosin light chain kinase (cMLCK), Protein Phosphatase type 1 (PP1 ... The receptors for all NRG1 isoforms are the ERBB family of tyrosine kinase transmembrane receptors. Through their displayed ... and functional integrity of the heart. NRG-1 and its receptor family ErbB can play a beneficial role in the treatment of ... as a 44-kD glycoprotein that interacts with the NEU/ERBB2 receptor tyrosine kinase to increase its phosphorylation on tyrosine ...
"Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo". The Journal of Cell Biology. 130 ( ... "The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha- ... "Entrez Gene: CDH1 cadherin 1, type 1, E-cadherin (epithelial)".. *^ Fleming TP, Papenbrock T, Fesenko I, Hausen P, Sheth B ( ... Wendeler MW, Praus M, Jung R, Hecking M, Metzig C, Gessner R (April 2004). "Ksp-cadherin is a functional cell-cell adhesion ...
II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine ... Src homology 2 domain-containing protein-tyrosine phosphatase 1 (SHP-1) is one of the tyrosine phosphatases activated by AT2 ... B2 indicates bradykinin B2 receptor; ETB, endothelin B receptor; D1/D2/D3, type 1/type 2/type 3 dopamine receptor. ... Trans-inactivation of receptor tyrosine kinases by novel angiotensin II AT2 receptor-interacting protein, ATIP. J Biol Chem. ...
Antibody, Protein tyrosine phosphatase receptor type, C, PTPRC, CD45R, Lymphocyte, leukemia, lymphoma Prof Irene Leigh ... PTPRC regulates the threshold of T cell antigen receptor (TCR) signaling through dephosphorylation of protein tyrosine kinases ... 351C5 may be used in the typing of leukaemias and lymphomas and in studies of functional subsets of B and T cells. ... 1- Mouse antibody against Protein tyrosine phosphatase, receptor type, C (PTPRC, CD45R) (Subclass: IgGM) ...
Protein Tyrosine Phosphatase Receptor Type G (PTPRG) Controls Fibroblast Growth Factor Receptor (FGFR) 1 Activity and ... Versatile approach for functional analysis of human proteins and efficient stable cell line generation using FLP-mediated ... Influences Sensitivity to FGFR Kinase Inhibitors. Kostas M, Haugsten EM, Zhen Y, Sorensen V, Szybowska P, Fiorito E, Lorenz S, ... Plasmid Article: A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells.. ...
Purchase G Protein Pathways, Part C: Effector Mechanisms, Volume 345 - 1st Edition. Print Book & E-Book. ISBN 9780121822460, ... Regulation of Mitogen-Activated Protein Kinases by G-Protein-Coupled Receptors. Analysis of Protein Kinase B/Akt. Direct ... Functional Analyses of Type V Adenylyl Cyclase. Photoaffinity Labeling of Adenylyl Cyclase. Crystallization of Complex between ... Section VII: Protein Kinases and Phosphatases: Analysis of c-Jun N-Terminal Kinase Regulation and Function. Double-Label ...
Physical and functional association of the Src family kinases Fyn and Lyn with the collagen receptor glycoprotein VI-Fc ... and the podoplanin receptor C-type lectin-like receptor 2 (CLEC-2).1-3 Classically, SFK activity is regulated by tyrosine ... Regulation of Src family kinases involved in T cell receptor signaling by protein-tyrosine phosphatase CD148. J Biol Chem. 2011 ... Dominant Role of the Protein-Tyrosine Phosphatase CD148 in Regulating Platelet Activation Relative to Protein-Tyrosine ...
Janus kinase/signal transducers and activators of transcription; CD45, protein tyrosine phosphatase, receptor type C/cluster of ... 2014). Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat. Neurosci. 17, 131- ... 1995). Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in ... Src homology 2-containing inositol phosphatase 1; BMP, bone morphogenetic protein; mTOR, mammalian target of rapamycin; NO, ...
Selective down-regulation of angiotensin II receptor type 1A signaling by protein tyrosine phosphatase SHP-2 in vascular smooth ... Mitogen-activated protein kinase activation by hydrogen peroxide is mediated through tyrosine kinase-dependent, protein kinase ... The functional significance of SHP-2 oxidation was evaluated by assessing signaling growth responses to Ang II in SHP-2 ... Protein tyrosine phosphatases play a critical role in the reversible phosphorylation of proteins, where they remove phosphates ...
... type II) (N6514) and Protein G Sepharose Fast Flow Beads (P3296) were purchased from Sigma-Aldrich. FastAP Thermosensitive ... Likewise, there may be cases where glycosylation of certain cell surface glycoproteins is altered but without a functional ... 13.3 μg/ml alkaline phosphatase and 2 μl Arthrobacter ureafaciens (AU) neuraminidase per reaction, with a reaction volume of ... Among the most affected receptors in the STT3A-null cells were the receptor tyrosine kinases INSR and IGF-1R. The levels of ...
Aims/hypothesis We determined the contribution to insulin resistance of the PH domain leucine-rich repeat protein phosphatase ( ... Defective insulin receptor tyrosine kinase in human skeletal muscle in obesity and type II (non-insulin-dependent) diabetes ... To determine the functional impact of PHLPP-1 overproduction in insulin-responsive cell lines, human hepatoma HepG2 cells and ... Insulin initiates its action by binding to the insulin receptor and activating its intrinsic tyrosine kinase. This event leads ...
... phosphatase and tensin homolog and protein tyrosine phosphatase, non-receptor type 11. In addition, administration of miR-130 ... Focal Adhesion Kinase Overexpression Enhances Ras-dependent Integrin Signaling to ERK2/Mitogen-activated Protein Kinase through ... Functional inhibition of PTPN11 either by using a dominant-negative mutant [28] or pharmacological inhibitor [29] leads to the ... phosphatase and tensin homolog deleted from chromosome 10; PTPN11: Tyrosine-protein phosphatase non-receptor type 11; UTR: ...
... or receptor tyrosine kinase-mediated and GEF-dependent RAS activation (such as by targeting the scaffolding phosphatase SHP2). ... Wild-type (WT) RAS proteins are guanosine triphosphate (GTP)-hydrolyzing proteins [guanosine triphosphatases (GTPases)] that ... Despite the similar functional consequences of these mutations, they are found at disparate frequencies among cancer types and ... As expected, they found that G12Ci lethality was enhanced by silencing upstream components of receptor tyrosine kinase (RTK)- ...
... protein kinase A; PKC, protein kinase C; PLC, phospholipase C; PTP, protein tyrosine phosphatase; siRNA, small interfering RNA ... Mutation of tyrosines 492/493 in the kinase domain of ZAP-70 affects multiple T-cell receptor signaling pathways. J. Biol. Chem ... The functional role of S376 phosphorylation was addressed by comparing the ability of SLP-76-WT and SLP-76-S376A to complement ... Moreover, an SLP-76-S376A mutant induced higher interleukin 2 gene transcription than wild-type SLP-76. These data reveal a ...
Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs ... activating its GTPase activity and probably coupling the EGF receptor signaling to the G protein-coupled receptor signaling. ... The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. ... Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. ...
Protein Tyrosine Phosphatase δ Mediates the Sema3A-Induced Cortical Basal Dendritic Arborization through the Activation of Fyn ... Distribution and Properties of Functional Postsynaptic Kainate Receptors on Neocortical Layer V Pyramidal Neurons Matthias Eder ... Tyrosine Kinase Fumio Nakamura, Takako Okada, Maria Shishikura, Noriko Uetani, Masahiko Taniguchi, Takeshi Yagi, Yoichiro ... Cell-Type-Specific Contributions of Medial Prefrontal Neurons to Flexible Behaviors Hirofumi Nakayama, Ines Ibañez-Tallon and ...
... a Wnt receptor, is important for cell fate determination during corticogenesis. During neuronal differentiation, the Ryk ... Functional roles of protein phosphatase 4 in multiple aspects of cellular physiology: a friend and a foe. Park J, Lee DH. Park ... The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. During ... Publication types *. Research Support, N.I.H., Extramural Actions. * Search in PubMed ...
... protein expression, two markers highly specific of glioma stem cells, on a cohort of human paired glioblastoma samples ... Protein tyrosine phosphatase receptor type Z1 (PTPRZ1)-MET proto-oncogene receptor tyrosine kinase (MET) (ZM) fusion has been ... Whole-transcriptome sequencing profiling identifies functional and prognostic signatures in patients with PTPRZ1-MET fusion- ... Transmembrane protein 45A regulates the proliferation, migration, and invasion of glioma cells through nuclear factor kappa-B ...
Switching of the substrate specificity of protein tyrosine phosphatase N12 by cyclin-dependent kinase 2 phosphorylation ... The protein tyrosine phosphatase nonreceptor type 12 (PTPN12) is a multifunctional protein and has elicited much research ... FFAR2-FFAR3 receptor heteromerization modulates short-chain fatty acid sensing [Research]. Free fatty acid receptors 2 and 3 ( ... However, the functional significance of this phosphorylation is undefined. In the present study, we found that S19 site ...
receptor protein. tyrosine kinase adaptor. protein activity. intracellular. SH3/SH2 adaptor. cytoplasm. ... type I, beta, NM-001037.1); PSPH (phosphoserine phosphatase, NM-003832.1); GPATCH3 (G patch domain containing 3, NM-022078.1); ... This stage correlates with Stage 4 of the Functional Assessment Staging (FAST) scale or mild AD according to the criteria ... Protein kinase C (PKC) is one of the largest gene families of protein kinase (Liu and Heckman, Cell Signal. 1998; 10:529-542). ...
Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the PTPRF gene. The protein encoded by ... functional roles of the two intracellular phosphatase like domains of the receptor-linked protein tyrosine phosphatases LCA and ... "The multidomain protein Trio binds the LAR transmembrane tyrosine phosphatase, contains a protein kinase domain, and has ... "Entrez Gene: PTPRF protein tyrosine phosphatase, receptor type, F". Bonvini P, An WG, Rosolen A, Nguyen P, Trepel J, Garcia de ...
Various receptor-type tyrosine kinases, including the BDNF receptor TrkB, as well as Src family kinases (SFKs) mediate the ... an inhibitor of protein tyrosine phosphatase, to enhance protein tyrosine phosphorylation in the cells. Treatment of ... The functional relevance of tyrosine phosphorylation of Kvβ2 is unknown, although we identified Tyr25 as a major site of ... is an Ig-superfamily protein that undergoes tyrosine phosphorylation and binds the protein tyrosine phosphatase Shp2. Here we ...
Using the resource, we examined differentially expressed proteins between granulocyte, monocyte and dendritic cell subsets, and ... Using the resource, we examined differentially expressed proteins between granulocyte, monocyte, and dendritic cell subsets, ... Regulation of Src family kinases involved in T cell receptor signaling by protein-tyrosine phosphatase CD148. J Biol Chem. ( ... 1,492 proteins across multiple tissues (3) and 1,015 proteins that are expressed in one or more immune cell type and lymphoid ...
Estrogen receptor depletion reduced Trip10 expression by progressively increasing DNA methylation. We hypothesized that Trip10 ... Trip10 regulates cancer cell growth and death in a cancer type-specific manner. Differential DNA methylation of Trip10 can ... is a multi-domain adaptor protein involved in diverse cellular processes, which functions in a tissue-specific and cell lineage ... We previously found that Trip10 is highly expressed in estrogen receptor-expressing (ER+) breast cancer cells. ...
Genetic analysis reveals cell type-specific regulation of receptor tyrosine kinase c-Kit by the protein tyrosine phosphatase ... Isolation and functional characterization of human erythroblasts at distinct stages: implications for understanding of normal ... The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer. Nat Rev Cancer. 2014;14(12):769-785. ... Bypass mechanisms of resistance to receptor tyrosine kinase inhibition in lung cancer. Sci Signal. 2013;6(294):re6. ...
The immunomodulatory adapter proteins DAP12 and Fc receptor gamma-chain (FcRgamma) regulate development of functional ... ITIMs recruit tyrosine phosphatases, such as Src homology 2 domain tyrosine phosphatase (SHP) 1 and SHP-2, that negatively ... and the γ chain of the Fc receptor [FcRγ]), recruit tyrosine kinases (such as Syk or ZAP70) that trigger the activation of ... A number of putative fusion proteins have recently been identified in the plasma membrane of various types of fusing cells from ...
... which encodes the protein tyrosine phosphatase SHP-2, potentiate Ras signaling and are present in approximately 35% of sporadic ... GF, growth factor; RTK, receptor tyrosine kinase.. Validating mTOR dependence in vivo is an important next step, particularly ... Loss of the normal NF1 allele from the bone marrow of children with type 1 neurofibromatosis and malignant myeloid disorders. N ... Parkin and colleagues move from bedside to bench by identifying a subset of primary AML blast cells with absent functional NF1 ...
Cartilage matrix proteins, especially undegraded COL2, are shown to induce proteinases through a receptor tyrosine kinase ... 2004) Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females ... Article Type. Short Communication Publication history. Received date: May 02, 2016. Accepted date: May 23, 2016. Published date ... and alkaline phosphatase) by human osteoarthritic chondrocytes. Am J Pathol 159: 1777-1783. [Crossref] ...
... and lymphocyte-specific protein tyrosine kinase (LCK) kinases (data not shown). Sorafenib has been shown to inhibit JAK2 ... and that its phosphorylation is regulated by the tyrosine phosphatase PTPH1 in cultured cells (27) and the tyrosine kinases ... Tyrosine kinase inhibitors gefitinib, lapatinib and sorafenib induce rapid functional alterations in breast cancer cells. Curr ... Sorafenib primarily inhibits VEGF receptor (VEGFR), platelet-derived growth factor receptor (PDGFR), and Raf kinases, although ...
The tumor suppressor protein PTEN (phosphatase and tensin homologue deleted on chromosome 10), a dual specificity tyrosine- ... responding to single-agent gefitinib contain somatic mutations of unknown functional significance in the EGFR tyrosine kinase ... to ErbB-3 leading to PI3-K/Akt signaling activation only in NSCLC cell lines with either wild-type or mutant EGFR receptor and ... The protein kinase family has ,800 human members (11) among which receptor protein tyrosine kinases are frequently targets for ...
PTPN2 (protein tyrosine phosphatase non-receptor type 2 also known as TC-PTP) is a cytosolic tyrosine phosphatase that ... functions as a negative regulator of a variety of tyrosine kinases and additional signaling proteins. cells. In addition PTPN2 ... horseradish peroxidase type XII (5000 models), antifoam 204, -aminopropionitrile fumarate salt (BAPN), and 3,3,5,5- ... was identified as a negative regulator of NUP214-ABL1 kinase activity. Our study provides genetic and functional evidence for ...
We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their ... InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in ... is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of ...
  • Second, whereas potent and selective inhibitors of the RAF-MEK-ERK mitogen-activated protein kinase (MAPK) cascade have been developed to block this key RAS effector pathway, the development and efficacy of MEK inhibitors have been limited by resistance caused by the relief of ERK-mediated feedback inhibition, leading to compensatory reactivation of ERK. (
  • These phosphorylations recruit signal transducers leading to activation of signaling pathways that include the Ras/mitogen-activated protein kinase kinase/mitogen-activated protein kinase pathway, the signal transducers and activators of transcription pathway, and the PI3-K/Akt survival pathway. (
  • Today we know that this pathway constitutes the major oncogenic signaling axis next to the RAS/mitogen-activated protein kinase pathway. (
  • Previous reports indicated that LPS-induced mitogen-activated protein kinase activation is down-regulated by phosphatidylinositol 3-kinase through the activation of Akt. (
  • Furthermore, in HeLa cells dexamethasone induced the sustained expression of mitogen-activated protein kinase phosphatase 1 (MKP-1), a potent inhibitor of p38 function. (
  • Members of the three mitogen-activated protein kinase (MAPK) families mediate transcriptional and posttranscriptional changes in gene expression in response to proinflammatory stimuli (reviewed in references 15 , 25 , and 33 ). (
  • Extracellular signal-regulated kinase 2 (ERK2) is a member of the mitogen-activated protein kinase (MAPK) family of kinases activated in response to numerous growth factors and cytokines, leading to phosphorylation and functional regulation of downstream targets. (
  • Ras mediates its effect on cell proliferation mainly by activation of its effector Raf to initiate the mitogen-activated protein kinase (MAPK/extracellular signal regulated kinase [ERK]) cascade. (
  • Adenosine receptor, protein kinase G, and p38 mitogen-activated protein kinase-dependent up-regulation of serotonin transporters involves both transporter trafficking and activation. (
  • Human serotonin transporter variants display altered sensitivity to protein kinase G and p38 mitogen-activated protein kinase. (
  • Among the six known IRS proteins, IRS1 and IRS2 serve as adaptor proteins to both the insulin receptor (IR) and the IGF-1 receptor (IGF1R), activating the phosphatidylinositol 3-kinase and mitogen-activated protein kinase (MAPK) pathways ( 2 ). (
  • However, formation of the SIRP beta 1/DAP12 complex in myeloid cells induce tyrosine phosphorylation, mitogen-activated protein kinase activation, and cellular activation (5, 6). (
  • Furthermore, new insights have come from the growing appreciation that neither all RAS proteins (HRAS, NRAS, and KRAS4A/KRAS4B) nor all oncogenic RAS mutations (such as at residues Gly 12 , Gly 13 , and Gln 61 ) have the same impact on RAS signaling and function. (
  • The activating single missense mutations that have been found in human cancers occur primarily at codons encoding glycines at residues 12 (Gly 12 , commonly referred to clinically and per nomenclature as G12) and 13 (G13) or glutamine at residue 61 (Q61). (
  • Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues. (
  • They include the epidermal growth factor receptor (EGFR, ErbB-1, HER1), that when activated by ligand binding to its extracellular domain, homodimerizes or heterodimerizes with any of three other family members, ErbB-2 (HER2), ErbB-3 (HER3), and ErbB-4 (HER4), leading to autophosphorylation of cytoplasmic COOH-terminal tyrosine residues. (
  • Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (
  • Activation of MAPKs requires phosphorylation of both threonine and tyrosine residues within a Thr-Xxx-Tyr activation motif, where the central residue is glutamic acid in the case of the extracellular-signal-regulated kinase (ERK) family, proline in the case of the JNK family, and glycine in the case of the p38 family ( 15 , 25 , 33 ). (
  • In part this control is mediated by a family of about 12 dual-specificity phosphatases (DUSPs) or MAPK phosphatases (MKPs), which inactivate MAPKs by dephosphorylation of both threonine and tyrosine residues within the activation motif (reviewed in references 11 and 36 ). (
  • 8. The method of any one of claims 1- 7 , wherein the Aβ polypeptide is the major 42 amino acid long pathogenic Aβ protein, a shorter 40 amino acid long Aβ40 protein, or a longer C99 variant comprising the Aβ42 sequence, a fragment consisting of residues 25-35 of the full length Aβ protein, or the full length APP. (
  • Engagement of the IL-2R results in a cascade of signaling events initiated by phosphorylation of the tyrosine kinases Janus kinase 1 (JAK1) and JAK3 followed by phosphorylation of tyrosine residues on the IL-2R β-chain that results in phosphorylation of STAT5 and Shc. (
  • Protein phosphorylation on tyrosine residues is an important cell signaling mechanism that has a pivotal role in many biological processes, including cell proliferation, migration and transformation. (
  • For example, tyrosine phosphorylation is important for NMDA receptor gating, although it is unclear how many of the 25 or more tyrosine residues on the NR2A and NR2B C termini play specific biological roles ( 6 ). (
  • Phosphorylation by GSK-3 generally requires prior phosphorylation of a substrate by another kinase at a priming site four residues toward the C terminus from the phosphoacceptor site. (
  • Following ligand-binding to cell surface receptors, phosphorylates specific tyrosine residues on the cytoplasmic tails of the receptor, creating docking sites for STATs proteins. (
  • Positively charged residues within the transmembrane domain mediate interactions with DAP12 proteins which contain immunoreceptor tyrosine-based activation motifs (ITAMs) (3). (
  • The majority of well-known Ang II actions are mediated via AT 1 receptor stimulation, and angiotensin converting enzyme inhibitors (ACEI) and AT 1 receptor blockers (ARBs) have been widely used as antihypertensive drugs, with the expectation of cardiovascular protective effects. (
  • Epidermal growth factor receptor (EGFR) inhibitors such as gefitinib show antitumor activity in a subset of non-small cell lung cancer (NSCLC) patients having mutated EGFR. (
  • Recent work shows that phosphatidylinositol-3-kinase (PI3-K) is coupled to the EGFR only in NSCLC cell lines expressing ErbB-3 and that EGFR inhibitors do not inhibit PI3-K signaling in these cells. (
  • Lysyl oxidase (LOX) is the best characterized member of the family, with LDN193189 much known about its substrate specificity and inhibitors of enzymatic function (12,C19). (
  • The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [ PMID: 15078142 ], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [ PMID: 15320712 ]. (
  • Receptor tyrosine kinase inhibitors as potent weapons in war against cancers. (
  • Here, we discuss how therapy using PI3K pathway inhibitors could benefit from information on specific phosphatases, which naturally antagonize the kinase targets. (
  • Akt forms a complex with heat shock protein (Hsp) 90 and Cdc37, and inhibitors of Hsp90 cause Akt degradation. (
  • selective inhibitors of Akt kinase have not yet been reported. (
  • Resistance against epidermal growth factor receptor‑tyrosine kinase inhibitors (EGFR‑TKIs) develops following 8‑12 months of disease progression, and is a critical issue. (
  • In particular, EGFR-tyrosine kinase inhibitors (TKIs) have emerged as an alternative cancer treatment ( 2 - 4 ). (
  • Furthermore, we validated this approach by using specific kinase pathway inhibitors to perturb ABL1, FLT3, and JAK TK signaling in four xenografted patient samples. (
  • ATP-competitive AKT inhibitors failed to block the kinase-independent function of AKT, a liability that limits their effectiveness compared to allosteric AKT inhibitors. (
  • (2012) . Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. (
  • In an attempt to circumvent resistance to trastuzumab, anti-HER2 tyrosine kinase inhibitors (TKIs) were introduced. (
  • Assays and Characterization of Mammalian Phosphatidylinositol 4,5-Bisphosphate-Sensitive Phospholipase D. Characterization and Purification of Phosphatidylinositol Trisphosphate 5-Phosphatase from Rat Brain Tissues. (
  • Once phosphorylated, IRS proteins engage several proteins containing Src homology 2 domains, including the p85 regulatory subunit of phosphatidylinositol 3-kinase. (
  • Activated class I phosphatidylinositol 3-kinase generates the lipid phosphatidylinositol 3,4,5-trisphosphate. (
  • An important mechanism for increased cell survival in many cancers is mediated by the phosphatidylinositol-3-kinase (PI3-K)/Akt (protein kinase B) signaling pathway that is activated by receptor and oncogenic protein tyrosine kinases ( 2 ). (
  • Eight mammalian PI3-Ks are divided into three main classes: class I PI3-Ks phosphorylate membrane phosphatidylinositol to give PI(3, 4, 5)P 3 that recruits the cytoplasmic serine/threonine kinase Akt by binding to its pleckstrin homology domain. (
  • The phosphorylated ITAMs serve as docking sites for Src homology 2 domain-containing cytosolic proteins, including the tyrosine kinase Syk, the Ras adapter Shc, and the p85 subunit of phosphatidylinositol (PtdIns) 3-kinase. (
  • The phosphatidylinositol 3′-kinase/Akt pathway is activated frequently in human cancer, and has been implicated in tumor proliferation, cell survival, and resistance to apoptotic stimuli. (
  • Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. (
  • The receptor-mediated activation of the hydrolysis of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5) P 2 ] with the resultant production of inositol 1,4,5-trisphosphate (InsP 3 ) and diacylglycerol (DAG), the two second messengers linked to Ca 2+ signaling and protein-kinase-C-mediated phosphorylations, respectively, had become textbook knowledge by the early 90s. (
  • FAK, a non-receptor tyrosine kinase, interacts with a pool of intracellular signaling proteins, including c-Src, phosphatidylinositol 3-kinase (PI3-K), Rho GTPase family members, Grb2, and p130 CAS (6). (
  • PTEN is a tumor suppressor gene that belongs to the PTP superfamily and exhibits lipid phosphatase activity with high selectivity for the 3-position of phosphatidylinositol(3,4,5)trisphosphate. (
  • In addition, a variety of Ras effectors have been identified, such as a phosphatidylinositol 3-kinase (PI3K). (
  • AKT is a family of serine/threonine kinases consisting of three isoforms (AKT1, AKT2 and AKT3), regulated upstream by the activation of phosphatidylinositol 3-kinases (PI3K) following growth factor stimulation. (
  • Recent advances have shown that phosphatidylinositol 3-kinase/v-akt murine thymoma viral oncogene homolog (PI3K/AKT) pathway alterations play an important role in the development of a variety of human carcinomas, including HCC [ 4 - 6 ]. (
  • Generally, the AKT cascade is activated by receptor tyrosine kinases, cytokine receptors, G protein-coupled receptors, and other stimuli that induce the production of phosphatidylinositol-3,4,5-triphosphates [PI(3 ,4 ,5 )P3 ] by PI3K [ 11 ]. (
  • 1-3 In hypertension, increased ROS production leads to vascular smooth muscle cell (VSMC) growth and inflammation through increased activation of c-Src, mitogen-activated protein (MAP) kinases, and PI3K/AKT. (
  • As a result, therapeutic efforts have also focused on targeting downstream components of the Ras pathway, for example, Raf/MEK/extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K)/AKT/mTOR. (
  • mTOR is a serine-threonine kinase that functions downstream of Ras and PI3K/AKT, and mTOR has been shown to be negatively regulated by NF1 ( 8 ). (
  • Fast progress in sequencing technology has afforded us with landmark genetic alterations, which had immediate impact on clinical science and practice by pointing to new kinase targets, such as phosphoinositide 3-kinase (PI3K), the EGF receptor, or BRAF. (
  • Lipid-level phosphatases, such as PTEN and INPP4B, revert PI3K activity to keep the lipid second messengers inactive. (
  • Upon completion of this activity, the participant should have a better understanding of the lipid and protein phosphatases that regulate the PI3K pathway and their potential application as biomarkers to improve patient stratification, prediction of therapeutic responses, and disease outcomes in patients with cancer. (
  • Core phosphatases of the PI3K pathway. (
  • In cancer cells harboring gain-of-function alterations in MET, HER2, or Phosphatidyl-Inositol-3-Kinase (PI3K), catalytically inactive AKT (K179M) protected from drug induced cell death in a PH-domain dependent manner. (
  • Recent studies have shown that multiple phosphatases deactivate the PI3K/AKT signaling pathway. (
  • The PI3K/AKT pathway is a key signal transduction system that links oncogenes and multiple receptor classes to many essential cellular functions, and PI3K/AKT pathway activation promotes HCC cell tumorigenicity [ 7 - 9 ]. (
  • For example, an AT 1 /AT 2 chimeric receptor-study showed that substitution of IC3 in the AT 1 receptor failed to induce AT 1 receptor function via Gq protein coupling, 11 and also revealed that IC3 is a critical determinant of the mutually antagonistic AT 1 and AT 2 receptor signaling pathways. (
  • Studies of Endogenous G-Protein-Mediated Pathways in Neurons by Whole-Cell Electrophysiology. (
  • A molecular model explaining this functional flexibility posits that the intensity and duration of peptide/MHC stimuli impact the qualitative and/or quantitative composition of the TCR-proximal signaling machinery, triggering activation of all or part of a complex array of immediate signaling pathways ( 1 ). (
  • Phosphorylation of tyrosines on LAT and SLP-76 allows recruitment of effectors that channel signals to downstream pathways. (
  • Finally, the richness of phosphorylation-dependent signaling pathways in worms is further supported with the identification of 185 protein phosphatases and 128 phosphoprotein-binding domains (SH2, PTB, STYX, SBF, 14-3-3, FHA, and WW) in the worm genome. (
  • This induces EGFR tyrosine kinase activity, which subsequently triggers downstream signaling pathways ( 4 , 8 ). (
  • Stimulation of lymphocytes through multichain immune recognition receptors activates multiple signaling pathways. (
  • Adaptor proteins play an important role in integrating these pathways by their ability to simultaneously bind multiple signaling components. (
  • However, available data indicate that signaling pathways used by natural cytotoxicity receptors are largely similar to those used by the FcR. (
  • The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (
  • Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. (
  • In the 20 years since Paul Simpson initially demonstrated that neurohormonal stimulation of cultured neonatal cardiomyocytes results in cellular hypertrophy, characteristic changes in cardiac gene expression, and activation of specific kinase signaling pathways ( 1 - 3 ), protein kinases have attracted attention as candidate mediators of the cardiac biomechanical stress and trophic responses. (
  • Attempts to further define the signaling pathways for cardiac eutrophy, physiological hypertrophy, and pathological hypertrophy have employed a reductionist approach, delineating downstream signaling effectors of each receptor-hormone system and their specific manipulation in tissue culture or in physiologically stressed and genetically modified animal models. (
  • Through this receptor, Ang II activates a number of cytoplasmic signaling pathways. (
  • In this review, we describe detailed mechanisms of signal transduction pathways of Ang II involving small G proteins in VSMCs together with their functional significances in mediating vascular remodeling. (
  • Whereas the early events causing resumption of meiosis in mammalian oocytes are still a matter of debate, at least two receptor-activated pathways have been shown to cause meiotic resumption in Xenopus oocytes. (
  • The current consensus is that, whereas both βarr isoforms can desensitize and internalize cardiac GPCRs, they play quite different (even opposing in certain instances) roles in the G protein-independent signaling pathways they initiate in the cardiovascular system, including in the myocardium. (
  • For example, in the same cell, insulin can control glycogen synthesis and Wnt can control β-catenin protein levels, both in a GSK-3-dependent manner but without crossover between the two pathways ( 10 ). (
  • Although AKAPs have been identified on the basis of their interaction with PKA, they also bind other signaling molecules, mainly phosphatases and kinases, that regulate AKAP targeting and activate other signal transduction pathways.We suggest that AKAP forms a "transduceosome" by acting as an autonomous multivalent scaffold that assembles and integrates signals derived from multiple pathways. (
  • G protein-coupled receptors ( GPCRs ), also known as seven-(pass)-transmembrane domain receptors , 7TM receptors , heptahelical receptors , serpentine receptor , and G protein-linked receptors ( GPLR ), constitute a large protein family of receptors that detect molecules outside the cell and activate internal signal transduction pathways and, ultimately, cellular responses. (
  • The insulin receptor substrate (IRS) proteins are key molecules in the signaling pathways induced by insulin and insulinlike growth factor 1 (IGF-1) and mediate their pleiotropic effects, including cell growth, survival, development and glucose metabolism ( 1 ). (
  • Acts downstream of various receptor and cytoplasmic protein tyrosine kinases to participate in the signal transduction from the cell surface to the nucleus. (
  • These signals regulate the activities of cytoplasmic kinases, growth factor receptors, and ion channels and control the organization of the intracellular actin cytoskeleton. (
  • Hence, integrins transduce signals by associating with adapter proteins that connect the integrin to the cytoskeleton, cytoplasmic kinases, and transmembrane growth factor receptors. (
  • STATs (signal transducers and activators of transcription) are a family of latent cytoplasmic proteins that are activated to participate in gene control when cells encounter various extracellular polypeptides. (
  • 35) interact with specific cell surface receptors that trigger the activation of latent cytoplasmic transcription factors termed STATs. (
  • a and a ß subunit, with a long extracellular domain binding to the ECM, a transmembrane domain, and a short cytoplasmic domain that associates with the actin cytoskeleton and adaptor proteins (3). (
  • Phosphorylation occurs within the cytoplasmic tails of the β and γ subunits in a domain that encodes the immunoreceptor tyrosine-based activation motif (ITAM), which is characterized by a YXXL-X 7 -YXXL amino acid sequence ( 4 ). (
  • For example, cell stimulation with erythropoietin (EPO) during erythropoiesis leads to JAK2 autophosphorylation, activation, and its association with erythropoietin receptor (EPOR) that becomes phosphorylated in its cytoplasmic domain. (
  • SIRP beta 1 has a relatively short cytoplasmic region and lacks the signaling motifs for association with phosphatases. (
  • Authors: Chen BS, Wang KY, Yu SQ, Zhang CB, Li GZ, Wang ZL, Bao ZS Abstract Gliomas are the most common type of primary brain tumor in adults with a high mortality rate. (
  • Activating mutations in RAS proteins are found in ~24% of all cancers [as reported in the Catalog of Somatic Mutated in Cancer (COSMIC) database, v89] and are commonly associated with resistance to frontline therapies ( 1 ). (
  • Despite the similar functional consequences of these mutations, they are found at disparate frequencies among cancer types and among RAS genes. (
  • These findings suggest that the different RAS isoforms, as well as individual mutations within one RAS protein, have distinct properties despite their high sequence similarity and conserved function. (
  • Children with Neurofibromatosis type 1, a dominant familial cancer syndrome, have germline inactivating mutations in NF1 , and are at markedly increased risk of developing JMML ( 6 ). (
  • Activating mutations in PTPN11 , which encodes the protein tyrosine phosphatase SHP-2, potentiate Ras signaling and are present in approximately 35% of sporadic JMML. (
  • In AML, activating somatic mutations in the FLT3 tyrosine kinase result in deregulated Ras signaling ( 5 ). (
  • More often, activation of Akt in tumors results from upstream induction by overexpressed tyrosine kinases or mutations in genes that encode proteins that directly regulate its activity. (
  • Activating mutations in EGFR are able to activate tyrosine kinase in the absence of ligands. (
  • The two most commonly observed mutations are exon 19 deletions and L858R missense substitutions at position 858, accounting for 60 and 35% of the total cases, respectively ( 12 , 13 ). (
  • Activating mutations in tyrosine kinases (TK) drive pediatric high-risk acute lymphoblastic leukemia (ALL) and confer resistance to standard chemotherapy. (
  • Most cases of NSML are caused by catalytically inactivating mutations in the protein tyrosine phosphatase (PTP), non-receptor type 11 (PTPN11), encoding the SH2 domain-containing PTP-2 (SHP2) protein. (
  • Additional point mutations or intragenic deletions of GLRA4 as well as functional studies are needed to further validate our hypothesis. (
  • Primary immunodeficiencies caused by mutations in actin regulatory proteins. (
  • Therefore, we examined associations between 522 single nucleotide polymorphisms and seven KIT or PDGFRA tumor mutations types. (
  • Other noteworthy associations included rs3024498 ( IL10 ) and rs1050783 ( F13A1 ) with PDGFRA mutations, rs2071888 ( TAPBP ) with wild type tumors and several matrix metalloproteinase SNPs with KIT exon 11 codon 557-558 deletions. (
  • Such mutations can enable receptor activation in the absence of normal stem cell factor signaling mechanisms, thereby over-stimulating cell proliferation and leading to tumor development. (
  • UNLABELLED: Activation of the epidermal growth factor receptor (EGFR) in glioblastoma (GBM) occurs through mutations or deletions in the extracellular (EC) domain. (
  • When the TCR engages with antigenic peptide and MHC (peptide/MHC), the T lymphocyte is activated through signal transduction, that is, a series of biochemical events mediated by associated enzymes, co-receptors, specialized adaptor molecules, and activated or released transcription factors. (
  • Focal adhesion kinase (FAK) becomes tyrosine-phosphorylated during integrin-mediated cell adhesion and is believed to play important roles in integrin signal transduction (7,8). (
  • 5-8 Importantly, recent accumulating evidence highlighted the significance of these small G proteins as essential molecular switches that trigger many of the signal transduction and functions of Ang II. (
  • I will also discuss the challenges in simultaneously harnessing two types of molecular addictions for therapeutic benefit, and the importance of understanding not only the effects of oncogenic signal transduction on metabolism, but also the impact of metabolic states on signal transduction. (
  • It is crucial in lymphocyte development and antigen signaling, serving as an important regulator of Src-family kinases, promotes cell survival by modulating integrin-mediated signal transduction pathway and is also involved in DNA fragmentation during apoptosis. (
  • Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. (
  • Here, we show that a member of the Protein Phosphatase 2C (PP2C) family in Arabidopsis ( Arabidopsis thaliana ), PP2C5, is acting as a MAPK phosphatase. (
  • Thus, we suggest that PP2C5 acts as a MAPK phosphatase that positively regulates seed germination, stomatal closure, and ABA-inducible gene expression. (
  • The best-characterized effector of Ras is Raf, a MAPK kinase kinase, in the MAPK/ERK cascade. (
  • In this review, I will discuss the therapeutic opportunities that these two types of molecular addictions offer, focusing on lessons learned from targeting members of the epidermal growth factor receptor family of kinases, and components of MAPK pathway. (
  • Protein tyrosine kinase Syk is associated with and activated by the IL-2 receptor: possible link with the c-myc induction pathway. (
  • Moreover, genetic variations outside the MHC locus involving genes in type I interferon pathway, NF- κ B signaling, B- and T-cell function and methylation processes have been shown to be associated with both SS and SS-related lymphoma development. (
  • OBJECTIVE In humans, multiple genes in the interleukin (IL)-2/IL-2 receptor (IL-2R) pathway are associated with type 1 diabetes. (
  • These findings suggest novel targets for treatment of type 1 diabetes within the IL-2R pathway and suggest that an altered IL-2R signaling signature may be a biomarker for type 1 diabetes. (
  • Any process that initiates the activity of an inactive cysteine-type endopeptidase involved in the apoptotic signaling pathway. (
  • Alternatively additionally it is possible the fact that critical types regulating Aβ creation is certainly another lipid in the cholesterol biosynthetic pathway. (
  • It has been reported that LIF activates the AKT pathway in several different cell types, including human embryonic kidney 293T, liver Hep3B, and oligodendrocytes [7, 27]. (
  • LIF binds to its receptor complex composed of LIFR and gp130 to activate the LIF signaling pathway. (
  • It is currently unclear whether LIF activates the AKT-mTOR pathway to promote tumorigenesis and metastasis in other types of cancers. (
  • GskA, the Dictyostelium GSK-3 orthologue, is modified and activated by the dual-specificity tyrosine kinase Zak1, and the two kinases form part of a signaling pathway that responds to extracellular cyclic AMP. (
  • The discoidin 1 genes are positively regulated by the pathway, while the abundance of the H5 protein is negatively regulated. (
  • These proteins, ropporin (a protein previously shown to interact with the Rho signaling pathway) and AKAP-associated sperm protein, are 39% identical to each other and share a strong sequence similarity with the conserved domain on the N terminus of RII that is involved in dimerization and AKAP binding. (
  • PTPN2 regulates the Janus kinase/signal transducers and activators of transcription pathway by inhibiting signalling via the interleukin (IL)-2 receptor (CD122). (
  • Moreover, FS stress-induced tyrosine phosphorylation of both the NR2B subunit of the NMDA subtype of glutamate receptor and the K + -channel subunit Kvβ2 was regulated by SIRPα. (
  • FcγRI and IIIa are activating receptors, and are associated with low m.w. γ-subunit homodimers, which contain an immunoreceptor tyrosine-based activation motif (ITAM). (
  • Combined immunodeficiency due to a mutation in the ?1 subunit of the coat protein I complex. (
  • In an allergic reaction, mast cell activation is initiated through the recognition of an antigen (Ag) by antigen-specific IgE bound to the α subunit of the high affinity IgE receptor (FcεRI), which is expressed on the cell surface. (
  • Using this method, we were able to differentiate between distinct isoforms of Ca 2+ /calmodulin-dependent protein kinase (CaMKII) and identify a novel activity-regulated phosphorylation site on the glutamate receptor subunit GluR1. (
  • Proteomic analysis of human norepinephrine transporter complexes reveals associations with protein phosphatase 2A anchoring subunit and 14-3-3 proteins. (
  • Identification of sperm-specific proteins that interact with A-kinase anchoring proteins in a manner similar to the type II regulatory subunit of PKA. (
  • AKAPs contain an amphipathic helix domain that binds to the type II regulatory subunit of PKA (RII). (
  • The G protein's α subunit, together with the bound GTP, can then dissociate from the β and γ subunits to further affect intracellular signaling proteins or target functional proteins directly depending on the α subunit type ( G αs , G αi/o , G αq/11 , G α12/13 ). (
  • however, the third intracellular loop (IC3) of these receptors plays a pivotal role in signaling activation by both receptors. (
  • Another type of fusion occurs between distinct membranes within a cell, such as during intracellular trafficking between the endoplasmic reticulum and the Golgi apparatus. (
  • Fusion of an intracellular vesicle with its target membrane is mediated by a set of conserved proteins that are collectively referred to as SNAREs (soluble NSF-attachment protein [SNAP] receptors). (
  • PtdIn3,4,5P 3 , the lipid product of PtdIns3-kinase, is an important second messenger that is necessary for the activation of pleckstrin homology domain-containing enzymes such as the serine/threonine kinase Akt, the guanine nucleotide exchange factor Vav, and the Tec family tyrosine kinase Btk, involved in intracellular calcium mobilization ( 12 ). (
  • Another adaptor protein Src homology (SH) 2 domain-containing leukocyte protein of 76 kDa (SLP-76) ( 14 ) and its homologue B cell linker protein (BLNK)/SLP-65 ( 15 ) are involved in the activation of PLC-γ, an enzyme necessary for receptor-initiated increases in the concentration of intracellular calcium (reviewed in Ref. 16 ). (
  • These proteins are connected to intracellular proteins that include diverse signaling molecules recruited to sites of focal adhesion, and are also linked to the actin cytoskeleton (2). (
  • Interaction of integrins with the ECM proteins can induce tyrosine phosphorylation of many intracellular proteins. (
  • IP 3 binds to its receptors on the endoplasmic reticulum promoting calcium release from the intracellular stores, which upon emptying trigger calcium influx from the extracellular environment via store-operated calcium channels like Orai1/CRACM ( 6 , 7 ). (
  • It also activates various intracellular tyrosine and serine/threonine kinases. (
  • TCR engagement activates the protein tyrosine kinases Lck, Fyn, and ζ chain-associated protein of 70 kD that initiate the signaling cascade and contribute to the assembly of a "signalosome," a multiprotein complex including various enzymes, their substrates, and scaffold/adaptor proteins ( 4 ). (
  • The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. (
  • Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules. (
  • As a result of this interaction, the NK cell activates proximal Src ( 2 , 3 ) and Syk ( 4 , 5 ) family protein tyrosine kinases (PTKs), which in turn stimulate downstream effectors such as phospholipase C (PLC)-γ ( 6 , 7 ) and the Rho family of GTP-binding proteins ( 8 , 9 ). (
  • the second activates Bruton tyrosine kinase and Syk. (
  • Protein tyrosine phosphatases play a critical role in the reversible phosphorylation of proteins, where they remove phosphates from downstream substrates thereby counterbalancing effects of protein tyrosine kinases (PTK). (
  • In this report, we assessed the steady-state enzymatic activity of lysyl oxidase-like 2 (LOXL2) against the substrates 1,5-diaminopentane (DAP), spermine, and fibrillar type I collagen. (
  • Extracellular signal-regulated kinase 2 (ERK2) is an S/T kinase with more than 200 known substrates, and with critical roles in regulation of cell growth and differentiation and currently no membrane proteins have been linked to ERK2 scaffolding. (
  • The activation of Syk results in the phosphorylation of multiple substrates among which the membrane-localized linker for activation of T cells (LAT) coordinates the assembly of a molecular complex that includes proteins like phospholipase C (PLC)-γ. (
  • The serine-threonine kinase AKT regulates proliferation and survival by phosphorylating a network of protein substrates. (
  • Several downstream substrates of activated AKT play a major role in the regulation of cell size, cell cycle progression, glucose metabolism, genome stability, transcription, protein synthesis and inhibition of pro-apoptotic proteins [ 1-4 ]. (
  • Both are substrates for GSK-3 but can be phosphorylated by GSK-3 at different times, as phosphorylation is dependent on different priming kinases which are not coordinately regulated. (
  • The fusion of viruses with cells, in particular influenza virus and human immunodeficiency virus (HIV), provided strong evidence that fusion is mediated both by viral proteins and host cell surface molecules that function as viral receptors ( 3 ). (
  • Here, we present a comparative analysis of the enzymes and adaptor molecules that are the key components of the protein phosphorylation signaling network present in C. elegans . (
  • The T-cell receptor complex with TCR-α and TCR-β chains, CD3 and ζ-chain accessory molecules. (
  • The T-cell receptor , or TCR , is a molecule found on the surface of T cells , or T lymphocytes, [1] that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules. (
  • The TCR is a disulfide-linked membrane-anchored heterodimeric protein normally consisting of the highly variable alpha (α) and beta (β) chains expressed as part of a complex with the invariant CD3 chain molecules. (
  • Once phosphorylated, phospho-ITAMs constitute a novel docking site for the binding and subsequent activation of Src homology 2 (SH2)-domain containing molecules, such as the spleen tyrosine kinase (Syk), a tyrosine kinase that is crucial for mast cell activation ( 5 ). (
  • In this regard, Ras and Rho G proteins are the most investigated molecules in the cardiovascular system. (
  • Controlling both NK cell development and effector function is a variety of interactions between NK cell receptors and their ligands [6] , the class I molecules of the major histocompatibility complex (MHC): called the HLA complex in humans. (
  • At the molecular level, the addition or removal of a phosphate residue can considerably affect the function and/or localization of proteins including enzymes, ion channels, scaffolding proteins, or signaling molecules. (
  • The ligands that bind and activate these receptors include light-sensitive compounds, odors , pheromones , hormones , and neurotransmitters , and vary in size from small molecules to peptides to large proteins . (
  • Inset: TCR/MHC-peptide interactions with the support of adhesion molecules form microclusters that exclude CD45 and trigger robust tyrosine phosphorylation. (
  • E ) Neural synapses are stabilized by adhesion molecules and can recruit receptor tyrosine kinases. (
  • The tumor suppressor protein PTEN (phosphatase and tensin homologue deleted on chromosome 10), a dual specificity tyrosine-threonine/PI-3 phosphatase, prevents the accumulation of PI(3,4,5)P 3 and attenuates PI3-K signaling ( 9 ). (
  • Dual specificity protein kinases (e.g. (
  • The two teams immediately saw that the gene encodes a phosphatase, which launched a flurry of investigations for its substrate. (
  • The specific activity of ab268410 was 12 nmol/min/mg in a peptide kinase assay using Poly (4:1 Glu, Tyr) as substrate. (
  • 13. The method of any one of claims 1- 12 , wherein the amount of phosphorylated substrate polypeptide is determined by ELISA. (
  • Protein tyrosine phosphorylation is regulated in the cell by the opposing activities of two enzymes: protein tyrosine kinases (PTKs), which transfer phosphate from ATP to substrate proteins, and protein tyrosine phosphatases (PTPs), which remove it. (
  • A cDNA coding for PTPN13 was isolated during the screening for the substrate of protein kinase A expressed in mammalian oocytes. (
  • PTPN13 is expressed in both mouse and Xenopus oocytes and is a substrate for protein kinase A in vitro and in vivo. (
  • Substrate specificity can be determined by the identity and activation profile of the priming kinase, such as in the case of CRMP-2 and CRMP-4 ( 8 ). (
  • In addition, GSK-3 and its priming kinases may be brought into close contact with its substrate through the action of scaffold proteins, such as Axin, a protein which brings together the kinases CK1 and GSK-3 with their substrate β-catenin. (
  • This phosphorylation event is not required for kinase activity but may influence substrate interaction with the active site ( 9 ). (
  • The insulin receptor substrate (IRS) proteins are key mediators of insulin and insulinlike growth factor 1 (IGF-1) signaling. (
  • PTPRC regulates the threshold of T cell antigen receptor (TCR) signaling through dephosphorylation of protein tyrosine kinases (e.g. (
  • For instance, LAT binds phospholipase C (PLC)-γ1 ( 5 ), which regulates Ca 2+ - and diacylglycerol-dependent events (e.g., activation of the NFAT transcription factor and protein kinase C [PKC]), and Grb2, which recruits the Ras-specific activator SOS or the E3-ubiquitin ligase Casitas B lineage lymphoma proto-oncogene ( 8 ). (
  • Trip10 regulates cancer cell growth and death in a cancer type-specific manner. (
  • The calcium signal regulates multiple other enzymes, transcription factors, and cytoskeletal proteins. (
  • This work characterizes a new type of scaffolding complex, which we term a "shuffle complex", between the disordered hNHE1-tail and ERK2, and provides a molecular mechanism for the important ERK2 scaffolding function of the membrane protein hNHE1, which regulates the phosphorylation of both hNHE1 and ERK2. (
  • Ligand engagement both regulates and, in turn, is regulated by the level of activity of the kinase domain. (
  • We have identified PTPN14 as a YAP-binding protein that negatively regulates YAP activity by controlling its localization. (
  • GSK-3 is a multifunctional serine/threonine protein kinase that regulates a large number of key eukaryotic cellular processes, including intermediate metabolism, cytoskeleton maintenance, and development ( 12 ). (
  • Previous physiological and pharmacological experiments have demonstrated that the Chlamydomonas flagellar axoneme contains a cAMP-dependent protein kinase (PKA) that regulates axonemal motility and dynein activity. (
  • Lck regulates early activation events after TCR engagement ( 10 ), thymic differentiation ( 11 ), Th1/Th2 differentiation ( 12 ), apoptosis ( 13 ), and homeostatic proliferation of naïve T-cells ( 14 ). (
  • Protein tyrosine phosphatase receptor type Z1 (PTPRZ1)-MET proto-oncogene receptor tyrosine kinase (MET) (ZM) fusion has been identified as a biomarker for sGBM that is involved in glioma progression, but the mechanism of gliomagenesis and pathology of ZM-negative sGBM has remained to be full. (
  • PTEN and INPP4B phosphatases inactivate PIP-lipid second messengers to prevent AKT activation. (
  • In this study, we have examined the role of the inositol 3-phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in FcγR-induced macrophage function. (
  • We demonstrate that in ex vivo murine peritoneal macrophages that are deficient in PTEN expression, FcγR-induced Akt and extracellular signal-regulated kinase phosphorylation are enhanced. (
  • However, PTEN did not seem to influence tyrosine phosphorylation events induced by FcγR clustering. (
  • Analyzing the molecular events leading to PTEN influence on LPS/Toll-like receptor 4 (TLR4) signaling, we found that LPS-induced activation of mitogen-activated protein kinases is suppressed in PTEN −/− cells. (
  • Zebrafish embryos lacking functional PTEN display hyperbranching, overgrowth of blood vessels, visualized in the tunk region in Tg(kdrl:gfp) background. (
  • We isolated null mutants of both PTEN genes and found that adult zebrafish with a single wild type PTEN allele develop hemangiosarcomas, blood-filled clusters of blood vessels with endothelial origin. (
  • Hematopoietic stem and progenitor cells (HSPCs) hyperproliferate and arrest during differentiation in embryos lacking functional PTEN, resulting in enhanced numbers of blood cell progenitors, but no mature blood cells. (
  • Crystal structure of the IL-2 signaling complex: paradigm for a heterotrimeric cytokine receptor. (
  • Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. (
  • Receptors to which JAKs are bound are often referred to as cytokine receptors. (
  • Cytokine receptor expression and signaling upon exposure to IL-2, IL-7, and IL-15 were determined by flow cytometry and Western blot analysis. (
  • In contrast, both Lyn A and B caused similar total cellular tyrosine phosphorylation and FcεRI phosphorylation and neither Lyn A nor Lyn B alone could completely restore mast cell degranulation or dampen the excessive cytokine production seen in the absence of Lyn. (
  • Both in human and in the NOD mouse model, peripheral T-cells are characterized by functional defects after T-cell receptor (TCR)-mediated lymphocyte activation, including a decreased proliferative response ( 3 , 4 ) and a biased T-helper (Th)-1 and Th2 cytokine profile ( 5 , 6 ). (
  • Reduced glycosylation of PCSK5a in STT3A -null cells or cells treated with the oligosaccharyltransferase inhibitor NGI-1 corresponded with failure to rescue receptor processing, implying that alterations in the glycosylation of this convertase have functional consequences. (
  • The decreased glucose tolerance caused by PX-866 was insensitive to the AMP-activated protein kinase inhibitor metformin but reversed by insulin and by the peroxisome proliferator-activated receptor-γ activator pioglitazone. (
  • Yet, because they occupy critical nodes in preventing cancer initiation and progression, the information on their status has tremendous potential in outcome prediction, and in matching the available kinase inhibitor repertoire with the right patients. (
  • Somatostatin (SST) was described initially as a secretory product of the hypothalamus acting as a potent inhibitor of GH secretion [ 12 ]. (
  • In addition, we observed an increase in fractional shortening (FS%) in SHP2Y279C/+ mice, an effect of increased compensatory hypertrophy, which was not apparent in SHP2Y279C/+ mice treated with ARQ 092, suggesting functional improvement of HCM upon treatment with the AKT inhibitor. (
  • Through a glycomics approach, we identified 30 proteins, including tissue inhibitor of metalloproteinase-1 (TIMP-1), as a target protein for GnT-V in human colon cancer cell WiDr. (
  • PTN is an inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ, which is mainly expressed in the central nervous system. (
  • Src kinase regulation by phosphorylation and dephosphorylation. (
  • PTP1B directly interacts with both IR and IGF1R and catalyzes the dephosphorylation of both tyrosine kinase receptors ( 30 , 31 ). (
  • Recently, new evidence has accumulated showing the existence of several novel receptor interacting proteins and various angiotensin II receptor activation mechanisms beyond the classical actions of receptors for Ang II. (
  • Receptor dimerization of Ang II receptors such as homodimer, heterodimer, and complex formation with other G protein-coupled receptors has also been focused on as a new mechanism of their activation or inactivation. (
  • Moreover, ligand-independent receptor activation systems such as mechanical stretch for the AT 1 receptor have also been revealed. (
  • Nonisotopic Methods for Detecting Activation of Small G Proteins. (
  • Whereas tyrosine phosphorylation is usually associated with enzyme activation, oxidation leads to PTP inactivation. (
  • Ang II, through ROS, induces activation of RTKs such as EGFR and PDGFR-β as well as nonreceptor tyrosine kinases, such as c-Src, which interact with numerous PTPs, including SHP-2, to regulate cell function. (
  • The role of the nonmutated, wild-type RAS proteins in the context of mutant RAS is increasingly considered to be targetable, with reports of strategies that directly disrupt either the RAS interaction with activating guanine nucleotide exchange factors (GEFs) or receptor tyrosine kinase-mediated and GEF-dependent RAS activation (such as by targeting the scaffolding phosphatase SHP2). (
  • The SH2 domain-containing leukocyte protein of 76 kD (SLP-76) is a pivotal element of the signaling machinery controlling T cell receptor (TCR)-mediated activation. (
  • These data reveal a novel negative feedback loop involving HPK-1-dependent serine phosphorylation of SLP-76 and 14-3-3 protein recruitment, which tunes T cell activation. (
  • Additional SH2 domain binding motifs in the N-terminal region of SLP-76, encompassing phosphorylated Y113, Y128, and Y145, recruit the adaptor Nck, the guanine-nucleotide exchange factor Vav-1 and the inducible T cell kinase, which regulate actin cytoskeleton reorganization and PLC-γ1 activation ( 9 ). (
  • FS stress induced marked tyrosine phosphorylation of SIRPα in the brain of wild-type mice through activation of Src family kinases. (
  • Activation of both Syk and PtdIns3-kinase has been shown to be critical for phagocytosis ( 9 , 10 , 11 ). (
  • The frequency of Akt activation in human tumors and the functional consequences of its activation suggest that its pharmacologic inhibition may be a useful therapeutic strategy. (
  • Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15. (
  • Whereas Arabidopsis plants depleted of PP2C5 show an enhanced ABA-induced activation of MPK3 and MPK6, ectopic expression of PP2C5 in tobacco ( Nicotiana benthamiana ) resulted in the opposite effect, with the two MAPKs salicylic acid-induced protein kinase and wound-induced protein kinase not being activated any longer after ABA treatment. (
  • The general FcR structure and the signaling cascade that leads to this cytotoxic response are in many ways similar to receptors and cascades involved in the activation of B and T cells through sIg and TCR, respectively. (
  • Activation of lymphocytes through MIRR uses multiple adaptor proteins. (
  • Feedback modulation of NE release occurs by activation of alpha2A and alpha2C adrenergic receptors (ARs) on sympathetic neurons. (
  • Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. (
  • A great deal of new information has accumulated about specificity in the activation of the STATs, about the functional domains of the proteins, and about the variety of their biologic functions both in development and in adults. (
  • Phosphorylation on a single tyrosine located around residue 700 in each protein is obligatory for STAT activation ( 1 , 2 ) (Fig. 1 ). (
  • Ligand-mediated dimerization of either type of receptor is believed to result in reciprocal tyrosine phosphorylation, and consequent activation, of the intrinsic or the attached kinase ( 6 ). (
  • Phosphorylation of the kinase is the first of three tyrosine phosphorylations culminating in STAT activation (Fig. 2 ). (
  • On the other hand, the controlled activation of Abl kinases is required for a large number of normal cellular processes. (
  • Prototypically, the growth factor receptor on activation recruits a Ras guanine nucleotide exchange factor (GEF), Sos, via adaptor proteins Shc and Grb2. (
  • Following B-cell receptor activation, 2 waves of tyrosine kinase phosphorylation occur. (
  • Recent accumulating evidence has suggested that the AT 2 receptor not only opposes the AT 1 receptor but also has unique effects beyond an interaction with AT 1 receptor signaling. (
  • On the other hand, recent experimental studies have also demonstrated the existence of proteins interacting with Ang II receptors by screening with a yeast-based 2-hybrid protein-protein interaction assay technique and revealed their functions ( Table ). (
  • 13 Although IC3 is well known as one of the most important domains of GPCRs for their interaction with G proteins, no interacting proteins with IC3 of both receptors have been reported to date. (
  • Recently, several GIPs have been reported to have unique roles in the regulation of AT 1 and AT 2 receptors via interaction with the C terminus of their receptors. (
  • Regulation of Latent Membrane Protein 1 Signaling through Interaction with Cytoskeletal Proteins. (
  • Functional Interaction of Ga13 with p115RhoGEF Determined with Transcriptional Reporter System. (
  • These diverse and sometime opposing roles of Trip10 may be due in part to splicing variants, but equally important, they could be the result of Trip10 interaction with distinct signaling partners in different cell types. (
  • Thus, a receptor-ligand interaction mediates the binding of viruses to the membrane of the host cell. (
  • Our results show that tyrosine-183 of 3BP2 is specifically involved in this interaction and that this residue critically influences 3BP2-dependent function. (
  • For example, Grb2, via its interaction with the guanine nucleotide exchange factor (GEF) Sos, links the GTP-binding protein Ras to upstream signaling complexes (reviewed in Ref. 13 ). (
  • Here, we identify the human Na + /H + exchanger 1 (hNHE1) as a membrane scaffold protein for ERK2 and show direct hNHE1-ERK1/2 interaction in cellular contexts. (
  • Comparison of the structural features of these domains not only reveals a high degree of conservation of their lipid interaction sites but also highlights their evolutionary link to protein modules known for protein-protein interactions. (
  • Biochemical and molecular genetic explorations have defined a single tyrosine phosphorylation site and, in a dimeric partner molecule, an Src homology 2 (SH2) phosphotyrosine-binding domain, a DNA interaction domain, and a number of protein-protein interaction domains (with receptors, other transcription factors, the transcription machinery, and perhaps a tyrosine phosphatase). (
  • The STATs become phosphorylated on tyrosine, then dimerize by reciprocal SH2 phosphotyrosine interaction and enter the nucleus to regulate transcription of many different genes. (
  • Lower panel: Protein interaction domains in the STATs listed at the left. (
  • Just as much as or even more than the Src kinases, Abl members are built to be able to couple protein-protein interaction with protein tyrosine kinase catalytic output. (
  • RNA-binding proteins are a large family of proteins with diverse functions which contain one or more RNA-binding domains (RBDs) and other auxiliary domains for protein-protein interaction and subcellular targeting ( 22 , 23 , 46 , 65 , 71 , 78 ). (
  • However, the PTPN14 PPxY motif and phosphatase activity appear to be dispensable for the negative regulation of endogenous YAP, likely suggesting more complex mechanisms of interaction and modulation. (
  • fyn -/- myotubes, focusing on clustering of postsynaptic proteins, their interaction with AChRs, and AChR phosphorylation. (
  • The cAMP-dependent protein kinase (PKA) is targeted to specific subcellular compartments through its interaction with A-kinase anchoring proteins (AKAPs). (
  • However, inhibition of the PKA catalytic activity does not mimic these peptides, suggesting that the peptides are disrupting the interaction of AKAP(s) with proteins other than PKA. (
  • The Protein Encoded by the CCDC170 Breast Cancer Gene Functions to Organize the Golgi-Microtubule Network. (
  • Moreover, an SLP-76-S376A mutant induced higher interleukin 2 gene transcription than wild-type SLP-76. (
  • This results in diversified gene expression profiles, making cells distinctively receptive to auxiliary environmental cues (e.g., cytokines and/or cell-cell interactions) and therefore shapes a particular functional behavior ( 2 , 3 ). (
  • Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the PTPRF gene. (
  • The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. (
  • Two alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. (
  • Reversible protein phosphorylation plays a central role in regulating basic functions of all eukaryotes such as DNA replication, cell cycle control, gene transcription, protein translation, and energy metabolism. (
  • Receptor-type tyrosine-protein phosphatase beta or VE-PTP is an enzyme specifically expressed in endothelial cells that in humans is encoded by the PTPRB gene. (
  • The synthetic glucocorticoid dexamethasone was demonstrated to inhibit p38 activity in a manner requiring ongoing, glucocorticoid receptor-mediated gene expression ( 40 ). (
  • SHP-1 (PTPN6) is one of the most important component from this equilibrium and decreased activity, gene mutation or gene deletion, leading to an increase in tyrosine-phosphorylated proteins in cells with pathological consequences [ 8 - 11 ]. (
  • MCG10 can be induced by wild-type but not mutant p53 and by DNA damage via two potential p53-responsive elements in the promoter of the MCG10 gene. (
  • The fragile X syndrome gene FMR1 encodes an RNA-binding protein with two KH domains ( 83 ). (
  • A mutation in the human norepinephrine transporter gene (SLC6A2) associated with orthostatic intolerance disrupts surface expression of mutant and wild-type transporters. (
  • The human lck gene, located on chromosome 1p35-34.3, was evaluated as a candidate susceptibility gene for type 1 diabetes. (
  • A molecular scan of the sequence variations in the coding, the relevant promoter, and most of the intronic sequences of the lck gene (representing a total of 10.5 kb fragment) was performed in 187 Caucasian subjects including 91 type 1 diabetic patients and 96 normoglycemic control subjects. (
  • The low frequency of these polymorphisms did not permit any statistically significant correlations with the disease status, suggesting that the lck gene probably does not contribute to genetic susceptibility to type 1 diabetes. (
  • The human lck gene, located on chromosome 1q35-34.3, has 12 exons distributed across ∼14 kb of genomic DNA. (
  • The lower protein expression in humans and the existence of a susceptibility region containing lck in the mouse model prompted us to test whether lck could be a new susceptibility gene for type 1 diabetes. (
  • A systematic survey of the natural sequence variation in the coding, the relevant promoter, and most of the intronic sequences of the lck gene was performed by direct sequencing in a cohort of healthy subjects ( n = 96) and type 1 diabetic patients ( n = 91). (
  • Ligand-activated receptors that catalyze this phosphorylation include receptors with intrinsic tyrosine kinase activity [for example, epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and colony-stimulating factor-1] as well as receptors that lack intrinsic tyrosine kinase activity but to which Janus kinases (JAKs) are noncovalently associated ( 3 , 6 ). (
  • Osteoprotegerin (OPG) is also suggested to prevent osteoarthritis progression through functional inhibition of its ligand TNF-related apoptosis-inducing ligand (TRAIL) [29]. (
  • For example, the HIV surface ligand gp120 binds to its receptor (CD4) on T lymphocytes and macrophages, and the hemagglutinin protein of influenza binds to its receptor (sialic acid) on epithelial cells. (
  • Yet, these observations still support the idea that receptor-ligand interactions are universally required for fusion. (
  • EGFR can be activated with ErbB receptors, either via autocrine or paracrine ligand binding. (
  • Integrin clusters in macromolecular complexes, ligand occupancy, and tyrosine phosphorylation are the key events that result in diverse processes such as cell migration and differentiation, tissue remodelling, cell proliferation, angiogenesis, and tumor cell invasion and metastasis (3,6). (
  • It is estimated that more than half of all drugs in clinical use target GPCRs, acting either to mimic endogenous GPCR ligands, to block ligand access to the receptor, or to modulate ligand production [ 1 ]. (
  • The three human RAS genes encode four highly identical proteins (83 to 85% identity): HRAS, NRAS, and KRAS4A and KRAS4B, with KRAS encoding splice variants due to alternative exon 4 utilization. (
  • In silico genome-wide analyses have shown that over 60% of all mammalian protein-coding genes are regulated by miRNAs [5,6]. (
  • The complexity of surface-expressed proteins, also called the surfaceome, is emphasized by the fact that an estimated 26% of human genes encode transmembrane proteins (~5,500) ( 1 ). (
  • ASO-mediated knockdown reproduced the published phenotypes for 8 developmental protein-coding genes ((((and was chosen as a test candidate because it is usually expressed both maternally and zygotically and has dosage-dependent phenotypes. (
  • Inside the CDR we found 28 genes downregulated, of which we selected three genes for further functional analysis: serin threonin kinase 4 (STK4), topoisomerase 1 (TOP1) and protein tyrosine phosphatase receptor T (PTPRT). (
  • In addition, we also included two additional candiate genes, V-MYB myeloblastosis viral oncogene homolog (avian)-like 2 (MYBL2) and L3MBTL, a human homolog of the Drosophila lethal (3) malignant brain tumor (D-l(3)mbt) polycomb protein, in the bone marrow transplantation experiments. (
  • However, proteomic and microarray analyses identified a number of proteins and genes, respectively, that are similarly misregulated in both mutant strains. (
  • The exact size of the GPCR superfamily is unknown, but at least 831 different human genes (or ~ 4% of the entire protein-coding genome ) have been predicted to code for them from genome sequence analysis . (
  • Genetic susceptibility to type 1 diabetes reflects the combined effect of multiple polymorphic genes interacting with environmental events ( 1 ). (
  • These emerging concepts of regulation of Ang II receptors and a new insight into future drug discovery are discussed in this review. (
  • Chaperone-Mediated Regulation of Choline Acetyltransferase Protein Stability and Activity by HSC/HSP70, HSP90, and p97/VCP. (
  • Expression and Characterization of Rat Brain Phospholipase D. G-Protein-Coupled Receptor Regulation of Phospholipase D. Analysis and Quantitation of Ceramide. (
  • We propose that Ang II induces phosphorylation of growth signaling kinases by redox-sensitive regulation of protein tyrosine phosphatases (PTP) in VSMCs and that augmented Ang II signaling in spontaneously hypertensive rats (SHRs) involves oxidation/inactivation and blunted phosphorylation of the PTP, SHP-2. (
  • Thus, tyrosine phosphorylation of SIRPα is important for regulation of depression-like behavior in the response of the brain to stress. (
  • Accordingly, recent advances in this area demonstrated that phagocytosis is a highly regulated process involving negative regulation by protein tyrosine phosphatases as well as inositol phosphatases ( 2 , 3 , 4 , 5 , 6 ). (
  • Recently, progress has been made in the elucidation of the regulation of clade A phosphatases. (
  • Adaptor proteins play a critical role in the regulation of multiple cellular functions such as proliferation, transcriptional regulation, and reorganization of the cytoskeleton (reviewed in Ref. 12 ). (
  • Protein-protein interactions involving lipid-binding domains could serve as the basis for phosphoinositide-induced conformational regulation of target proteins at biological membranes. (
  • Hantschel O, Superti-Furga G. Regulation of the c-Abl and Bcr-Abl Tyrosine Kinases. (
  • Pendergast AM. The Abl family kinases: Mechanisms of regulation and signaling. (
  • Mayer BJ, Baltimore D. Mutagenic analysis of the roles of SH2 and SH3 domains in regulation of the Abl tyrosine kinase. (
  • Extracellular matrix proteins and cell adhesion receptors (integrins) play essential roles in the regulation of cell adhesion and migration. (
  • Recently, two types of signaling by integrins have been extensively discussed: transmission of signals into the cell following binding of ligands or counter-receptors to the integrins (outside-in signaling), and regulation of the avidity and conformation of integrins by signals generated by other receptors within the cell (inside-out signaling) (5). (
  • Protein tyrosine phosphatase nonreceptor type 13 (PTPN13) is a tyrosine phosphatase with multiple interacting domains that has been implicated previously in the regulation of apoptosis. (
  • Several ribosomal proteins are RNA-binding proteins, for example, S6, S15, and L11, which are necessary for ribosome assembly and may be a target for translational regulation ( 23 , 82 ). (
  • GPCRs function in neurotransmission, neuroendocrine control of physiologic homeostasis and reproduction, and regulation of hemodynamics and intermediary metabolism, and they control the growth, proliferation, differentiation, and death of multiple cell types. (
  • Activity-dependent protein phosphorylation is one of the most ubiquitous and vital biochemical processes that contributes to the regulation and fine tuning of numerous cellular functions in many cell types. (
  • Wnt signaling can disrupt this protein complex to block β-catenin phosphorylation in a manner that is distinct from the regulation via serine phosphorylation at the N terminus of GSK-3 seen in response to signals such as insulin ( 24 ). (
  • IRS2 also coordinates IGF-1/IGF1R signaling in the central nervous system, where this factor is essential for the regulation of cell proliferation, growth, differentiation and metabolic demands during fetal and postnatal development ( 12 ). (
  • In addition to posttranslational modification by oxidation, PTPs are regulated by tyrosine (or serine) phosphorylation, 12 which renders the protein active. (
  • VE-PTP contains an extracellular domain composed of multiple fibronectin type_III repeats, a single transmembrane segment and one intracytoplasmic catalytic domain, thus belongs to R3 receptor subtype PTPs. (
  • Cellular protein phosphotyrosine levels are regulated by the antagonistic activities of the protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs). (
  • Background Protein tyrosine phosphatases (PTPs) play critical roles in human autoimmunity. (
  • 12 In the AT 2 receptor, IC3 is also important for its function involving reduction of SHP-1 activity and inhibition of extracellular signal regulated kinase (ERK) activity, and AT 2 receptor-induced apoptosis. (
  • Collectively, our findings show that STT3A-dependent inhibition of N-linked glycosylation on receptor tyrosine kinases and their convertases combines to impair receptor processing and surface localization. (
  • This inhibitory effect involves direct interactions of the glucocorticoid receptor with transcription factors such as NF-κB and AP-1, resulting in the inhibition of their function (reviewed in references 1 and 47 ). (
  • Modulation of sympathetic neuron signaling occurs by feedback inhibition of neurotransmitter release (autoreceptors), mediated in part via alpha2A and/or alpha2C adrenergic receptors. (
  • The Abl family of tyrosine kinases is regulated by a complex set of intramolecular interactions that impinge both directly and indirectly on the Abl kinase domain and lead to effective inhibition of tyrosine kinase activity both in vitro and in vivo. (
  • We show for the first time that IRS2 is essential for hearing and that PTP1B inhibition may be useful for treating deafness associated with hyperglycemia and type 2 diabetes. (
  • Recently, it has been shown that the diabetic phenotype in IRS2-deficient mice can be reverted by the inhibition of the protein tyrosine phosphatase (PTP)-1B ( 28 , 29 ). (
  • Diversifying these functions within individuals and populations are rapidly-evolving interactions between highly polymorphic major histocompatibility complex (MHC) class I ligands and variable NK cell receptors. (
  • An early study based on available DNA sequence suggested that the human genome encodes roughly 750 G protein-coupled receptors, [17] about 350 of which detect hormones, growth factors, and other endogenous ligands. (
  • We investigated by immunohistochemistry the clinical significance and the evolution of Oligodendrocyte lineage transcription factor 2 (OLIG2) and cyclin D2 (CCND2) protein expression, two markers highly specific of glioma stem cells, on a cohort of human paired glioblastoma samples comparing initial resections with recurrent tumors after radiation therapy alone or radio ‐chemotherapy with temozolomide according to the Stupp regimen. (
  • A more in-depth analysis has been performed on the 535 worm proteins containing zinc-binding domains, including the C4, C2H2, and C3HC4 ring finger types ( 3 ), and on the 83 worm homeobox transcription factors ( 4 ). (
  • HER2), BRAF, signal transducer and activator of transcription 3, AXL receptor tyrosine kinase and the amplification of CRK like proto-oncogene adaptor protein ( 19 - 25 ). (
  • In some individuals, decreased signal transducer and activator of transcription 5 phosphorylation correlated with significantly higher expression of protein tyrosine phosphatase N2, a negative regulator of IL-2R signaling. (
  • The activated AKT further phosphorylates multiple downstream effectors, such as glycogen synthase kinase-3 (GSK3α/β) and forkhead transcription factor (FoxO) family members, which together transmit potent growth, proliferation, and survival signals to cells [ 12 - 14 ]. (
  • Signal regulatory protein α (SIRPα) is an Ig-superfamily protein that undergoes tyrosine phosphorylation and binds the protein tyrosine phosphatase Shp2. (
  • A number of putative fusion proteins have recently been identified in the plasma membrane of various types of fusing cells from different species, many of which belong to the immunoglobulin superfamily of proteins (see reference 5 for a review). (
  • This superfamily represents the inter-SH2 domain found in ZAP-70 and SYK kinases. (
  • The small G proteins in this superfamily are structurally classified into ≥5 families: the Ras, Rho, Rab, Sar/Arf, and Ran families. (
  • The G protein-coupled receptors (GPCRs) or heptahelical or seven-transmembrane spanning receptors are by far the largest and most diverse superfamily of cell surface receptors. (
  • The importance of this receptor superfamily was highlighted last year by the awarding of the two pioneers of the field, Bob Lefkowitz and Brian Kobilka, with the Nobel Prize in Chemistry [ 2 ]. (
  • Signal-regulatory protein beta 1a (SIRP beta 1a) is a disulfide-linked type I membrane glycoprotein that belongs to the SIRP/SHPS (CD172) family of the immunoglobulin (Ig) superfamily. (
  • 1 Ang II binds 2 major receptors: the Ang II type-1 (AT 1 ) receptor and type-2 (AT 2 ) receptor. (
  • Adaptor proteins have no catalytic activity, but due to the presence of multiple phosphorylation sites and/or modular structure, they are able to physically bridge other signaling components. (
  • Membrane-associated Akt is activated by Ser 473 phosphorylation by membrane-associated phosphoinositide-dependent kinase-1 ( 3 ) and Thr 308 phosphorylation by a second incompletely characterized phosphoinositide-dependent kinase-2 ( 4 ). (
  • The phosphatase and tensin homolog phosphoinositide 3‑kinase signaling axis is a potential mechanism for acquiring resistance, and therefore targeting Bcl2 may be a useful strategy for further investigations. (
  • A new study now reveals an unexpected role for the receptor, dendritic cell-specific transmembrane protein (DC-STAMP), in this process. (
  • RPTPalpha is a transmembrane protein. (
  • Insulin initiates its action by binding to the insulin receptor and activating its intrinsic tyrosine kinase. (
  • Moreover, the miR-130-targeted LNA suppressed the phosphorylation of both FAK and Akt, resulting in the upregulation of two protein phosphatases, phosphatase and tensin homolog and protein tyrosine phosphatase, non-receptor type 11. (
  • Cartilage matrix proteins, especially undegraded COL2, are shown to induce proteinases through a receptor tyrosine kinase discoidin domain receptor 2 (DDR-2) [9-11]. (
  • We show reduced abundance of two canonical tyrosine receptor kinases - the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) - at the cell surface in STT3A -null cells, due to decreased N-linked glycan site occupancy and proteolytic processing in combination with increased endoplasmic reticulum localization. (
  • We determined the contribution to insulin resistance of the PH domain leucine-rich repeat protein phosphatase (PHLPP), which dephosphorylates Akt at Ser473, inhibiting its activity. (
  • Overexpression of PHLPP1 in HepG2 cells and L6 myoblasts resulted in impaired insulin signalling involving Akt/glycogen synthase kinase 3, glycogen synthesis and glucose transport. (
  • An increased expression level of this protein was found in the insulin-responsive tissue of obese, insulin-resistant individuals, and may contribute to the pathogenesis of insulin resistance. (
  • Insulin receptor protein-tyrosine phosphatases. (
  • Prospective evaluation of insulin and incretin dynamics in obese adults with and without diabetes for 2 years after Roux-en-Y gastric bypass. (
  • Protein tyrosine phosphatase (PTP)-1B dephosphorylates and inactivates both insulin and IGF-1 receptors. (
  • IRS2-deficient mice present altered hepatic insulin signaling and β-cell failure and develop type 2-like diabetes. (
  • As immunoglobulin proteins do not contain a fusion peptide or α-helical spring, these cannot be the universal tools that mediate membrane fusion. (
  • Protein phosphorylation is also required for more advanced functions in higher eukaryotes such as cell, organ, and limb differentiation, cell survival, synaptic transmission, cell-substratum and cell-cell communication, and to mediate complex interactions with the external environment. (
  • The effects of the matrix are primarily mediated by integrins, a family of cell surface receptors that attach cells to the matrix and mediate mechanical and chemical signals from it. (
  • Importantly, glycine receptors mediate inhibitory synaptic transmission in the brain stem as well as the spinal cord, and are known to be involved in syndromic intellectual disability. (
  • There are ≥2 transmembrane G protein-coupled receptors (GPCRs) known to mediate Ang II function, namely, the type 1 and type 2 (AT 1 and AT 2 ) receptors. (
  • The AT 1 receptor has been shown to mediate most of the physiological actions of Ang II, and this subtype is predominantly expressed in cardiovascular cells, such as VSMCs. (
  • NF1 encodes neurofibromin, a GTPase-activating protein and negative regulator of Ras. (
  • Determination of Strength and Specificity of Membrane-Bound G Protein-Phospholipase C Association Using Fluorescence Spectroscopy. (
  • Moreover, recruitment of multiple proteins containing PH domains binding to the same inositol lipid would create a large degree of information `spreading' and it is hard to see how cells could maintain signaling specificity if this were the case. (
  • Because aberrant protein phosphorylation is commonly the cause of cancer and other human diseases, a comprehensive knowledge of the key enzymes that regulate these functions can provide the basis for novel therapeutic intervention strategies. (
  • For example, the Src-family of protein-tyrosine kinases [ PMID: 15845350 ]. (
  • The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. (
  • Several global analyses of proteins and protein domains present in C. elegans have been presented elsewhere ( 1 - 4 ), revealing that protein kinases comprise the second largest family of protein domains in worms. (
  • VE-PTP is a member of the classical protein tyrosine phosphatase (PTP) family. (
  • 4 Upon receptor clustering by immune complexes, the tyrosines in the ITAM are phosphorylated by the membrane-associated Src family tyrosine kinases ( 8 ). (
  • Although sometimes considered to be within this family, the IL4 and IL7 receptors can form complexes with other receptor chains and are represented separately in Reactome. (
  • Receptors of this family associate with JAK1 and JAK3, primarily activating STAT5, although certain family members can also activate STAT1, STAT3 or STAT6. (
  • Integrins comprise a large family of cell surface receptors that are found in many animal species, ranging from sponges to mammals. (
  • This similarity led to the classification of surface Ig, TCR, and FcR into the family of so-called multichain immune recognition receptors (MIRR) ( 10 ). (
  • Evidence that has accumulated over the last years points to c-Abl and Arg (ABL1 and ABL2) as being particular forms of the Src family of kinases. (
  • Sicheri F, Moarefi I, Kuriyan J. Crystal structure of the Src family tyrosine kinase Hck. (
  • The Src family protein tyrosine kinase (Src PTK) Lyn provides the key recognition signal that inteprets receptor engagement into intracelluar events by transphosphorylating the FcεRI β and γ subunits ( 2 ). (
  • Specific to simian primates is the family of Killer cell Immunoglobulin-like Receptors (KIR), which recognize MHC class I and associate with a range of human diseases. (
  • We examined the role of Src-family kinases (SFKs) in vivo . (
  • cAMP-dependent protein kinase is targeted to discrete subcellular locations by a family of specific anchor proteins (A-kinase anchor proteins, AKAPs). (
  • In type 1 diabetic patients, the hyporesponsiveness of T-cells correlates with the low expression of Lck, a lymphoid protein tyrosine kinase of the Src family ( 7 ). (
  • The SIRP family are paired receptors that have similar extracellular domains but differing C-terminal domains and functions (1). (
  • Proteins in the SIRP family are typically expressed in cells of monocyte, macrophage or dendritic lineages (4). (
  • 14 These proteins mainly associate with the carboxyl (C) terminus of GPCRs and regulate their functions by trafficking, fine-tuning, and signaling modification. (
  • SIRPα was also found to regulate the FS stress-induced tyrosine phosphorylation of other neuronal proteins. (
  • We focus here on the content and diversity of protein kinases present in worms, together with an assessment of other classes of proteins that regulate protein phosphorylation. (
  • Recently, the 3BP2 adaptor protein has been shown to positively regulate the transcriptional activity of T cells. (
  • However, although MAPKs are known to regulate the action of several membrane proteins and receptors, none of these scaffold proteins are themselves membrane proteins, requiring additional mechanisms for colocalization of the scaffold protein, the membrane protein, as well as the kinases. (
  • We hypothesized that IQGAP1 could regulate TJ formation by modulating the expression and/or localization of junctional proteins, and we systematically tested this hypothesis in the model Madin-Darby canine kidney (MDCK) cell line. (
  • There are two main cell types that regulate neuroinflammation, namely astrocytes and microglia, the resident macrophages in the brain. (
  • SYK is a positive effector of B-cell antigen receptor (BCR) stimulated responses [ PMID: 19670961 , PMID: 19592646 ]. (
  • Bundling of information from multiple antigen receptor microclusters by an immunological synapse has parallels to bundling of multiple synaptic inputs into a single axonal output by neurons, allowing integration and coincidence detection. (
  • One of the Rho effectors, Rho-kinase (ROCK), plays an important role in actin cytoskeleton reorganization and smooth muscle contraction. (
  • The Cdc42-interacting protein-4, Trip10 (also known as CIP4), is a multi-domain adaptor protein involved in diverse cellular processes, which functions in a tissue-specific and cell lineage-specific manner. (
  • Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. (
  • Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation [ PMID: 12368087 ]. (
  • Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. (
  • Cellular localization is an important determinant of specialized function between homologous receptors. (
  • Using an array of molecular and cellular approaches and single cell amperometric analysis of neurotransmitter release, it should be possible to further delineate the interplay between protein structure, cellular localization, and physiological function of each receptor subtype. (
  • Transferrin receptor 1 is a cellular receptor for human heme-albumin. (
  • In this chapter, we provide an overview of the mechanisms by which multiple cellular proteins transiently activate Abl kinases to perform cellular functions. (
  • It consists of a set of kinases that, through a number of phosphorylation events, inactivate YAP, a transcriptional co-activator that controls cellular proliferation and apoptosis. (
  • Activity-dependent protein phosphorylation is a highly dynamic yet tightly regulated process essential for cellular signaling. (
  • In the nervous system, many proteins are known to be phosphorylated in an activity-dependent fashion in discrete cellular compartments. (
  • We identify potential cellular effectors for the two kinases by analyzing the corresponding null mutants. (
  • Over the previous decades, epidermal growth factor receptor (EGFR) has become a therapeutic target, as it triggers a signaling cascade that facilitates cell proliferation, survival and invasion. (
  • This PTP possesses an extracellular region, a single transmembrane region, and two tandem intracytoplasmic catalytic domains, and thus represents a receptor-type PTP. (
  • The extracellular region was shown to interact with the angiopoietin receptor Tie-2 and with the adhesion protein VE-cadherin. (
  • Using the resource, we examined differentially expressed proteins between granulocyte, monocyte, and dendritic cell subsets, and profiled dynamic expression of markers during thymocyte differentiation, T-cell maturation, and between functionally distinct B-cell subset clusters. (
  • In articular cartilage of osteoarthritis patients, pathologic expression of type X collagen (COL10) and other differentiation markers, including annexin VI, alkaline phosphatase, osteopontin, and osteocalcin, have been reported, [16-20] indicating that the osteoarthritis articular cartilage cannot maintain the characteristics of the permanent cartilage, but adds those of the embryonic or growth plate cartilage. (
  • Binding of IL-2 to the high-affinity IL-2R results in a wide range of biological responses including survival, differentiation, and proliferation of multiple cell types including T-cells. (
  • Non-receptor tyrosine kinase involved in various processes such as cell growth, development, differentiation or histone modifications. (
  • However, no link between IL-2 responsiveness and CD4 + CD25 + FOXP3 + regulatory T-cells (Tregs) has been demonstrated in type 1 diabetic subjects despite the role of these IL-2-dependent cells in controlling autoimmunity. (
  • Lyn B also showed increased binding of tyrosine phosphorylated proteins, which included the negative regulatory lipid phosphatase SHIP-1. (
  • A third, but less understood, regulatory mechanism is tyrosine phosphorylation at residue 216 (in GSK-3β). (
  • Oncogenic RAS proteins, which are mutated in approximately 24% of all human cancers, have earned a well-deserved reputation as being "undruggable. (
  • The functional consequences of recombinant PHLPP1 overexpression in hepatoma HepG2 cells and L6 myoblasts were investigated. (
  • Source of LOXL2 Protein Recombinant human LOXL2 was purchased from R & D Systems (Minneapolis, MN). (
  • Functional coding variation in recombinant inbred mouse lines reveals multiple serotonin transporter-associated phenotypes. (
  • CF stands for Carrier Free (CF). We typically add Bovine Serum Albumin (BSA) as a carrier protein to our recombinant proteins. (
  • Adding a carrier protein enhances protein stability, increases shelf-life, and allows the recombinant protein to be stored at a more dilute concentration. (
  • In general, we advise purchasing the recombinant protein with BSA for use in cell or tissue culture, or as an ELISA standard. (
  • Also, miR-3127 accelerated G1-S transition by activating AKT/ FOXO1 signaling, by directly targeting the 3′ untranslated regions (3`UTR) of pleckstrin homology domain leucine-rich repeat protein phosphatase 1/2 (PHLPP1/2), inositol polyphosphate phosphatase 4A (INPP4A), and inositol polyphosphate-5-phosphatase J (INPP5J) mRNA, repressing their expression. (
  • Various kinases are downstream effectors of neurohormone receptors that transduce signals from the sympathetic nervous and renin-angiotensin-aldosterone systems. (
  • Multiple downstream effectors of small G proteins, some of them being protein kinases, have been identified. (
  • Moreover, most of the available molecular insights are from structures of kinases in complex with folded domains or with small peptides of the scaffold proteins, and details regarding scaffolding by non-globular proteins are lacking. (
  • Here we review recent developments in the area of these cardiotrophic kinases, highlighting the utility of animal models that are helping to identify molecular targets in the human condition. (
  • Small GTP-binding proteins (G proteins) are monomeric G proteins with a low molecular weight of 20 to 40 kDa. (
  • A small G protein acts as a molecular switch that cycles between inactive GDP-bound and active GTP-bound forms. (
  • Preliminary data in cultured sympathetic ganglion neurons (SGN) and other cell types have found different temporal and spatial components to alpha2A&C AR localization and trafficking. (
  • 2-9 Therefore, recent advances in studies of Ang II receptors could prove the existence of a variety of new players and targets in addition to the traditional "Ang II world" and provide a new insight into cardiovascular biology. (
  • Here, we have summarized these emerging concepts concerning Ang II receptor interacting proteins and discuss new potent therapeutic targets in cardiovascular disease. (
  • 800 human members ( 11 ) among which receptor protein tyrosine kinases are frequently targets for cancer therapy. (
  • However, in contrast with their kinase counterparts the phosphatases are unlikely drug targets. (
  • Therefore, there is urgent need to characterize dysregulated TK signaling axes in patients with ALL and identify actionable kinase targets for the development of therapeutic strategies. (
  • By quantitatively assessing the tyrosine phosphorylation status of activated kinases in xenograft models of ALL, we were able to identify and validate clinically relevant targets. (
  • Therefore, this study highlights the application and potential of phosphotyrosine profiling for identifying clinically relevant kinase targets in leukemia. (
  • 1,2 Recently, small G proteins have been noted as novel therapeutic targets in cardiovascular medicine. (
  • Evidence from functional studies underlines the broad requirement for phosphorylation and the existence of many critical targets in nerve cells. (
  • In contrast, much less is known about how global defects in glycosylation, such as those found in many congenital disorders of glycosylation (CDG), alter the maturation, stability and function of receptors and other cell surface glycoproteins. (
  • The receptor-like tyrosine kinase (Ryk), a Wnt receptor, is important for cell fate determination during corticogenesis. (
  • Shp1 is expressed predominantly in hematopoietic cells, whereas Shp2 is expressed in most cell types including neurons. (
  • However, recent in silico evaluations predict that 2,886 proteins are actually expressed at the outer cell membrane, i.e., the cell surface ( 2 ). (
  • Experimental evidence exists for ~1,492 proteins across multiple tissues ( 3 ) and 1,015 proteins that are expressed in one or more immune cell type and lymphoid tissue ( 4 ). (
  • Differential DNA methylation of Trip10 can either promote cell survival or cell death in a cell type-dependent manner. (
  • Most of the viral proteins that are responsible for the binding of the virus to the host cell also play a role in fusion. (
  • For example, the attachment of HIV to its target cell via gp120 leads to a conformational change that exposes the associated fusion protein gp41 (gp120 and gp41 are derived from a single protein, gp160, that is posttranslationally cleaved). (
  • Most viral fusion proteins contain a stretch of hydrophobic amino acids, known as a fusion peptide, which penetrates host cells like a sword, destabilizing the lipid bilayer of the host cell. (
  • The fusion protein then undergoes a conformational change, forming a hairpin-like α-helical bundle, which acts like a spring to propel the viral membrane close enough to the cell membrane to trigger fusion. (
  • As thus far no two cell types share the same putative fusion protein, it seems plausible that alternative mechanisms for fusion might have evolved for each cell type, with fusion being cell type-specific and depending on different proteins in different species ( 5 ). (
  • T-cell responses to collagen type II, heat shock proteins and microbial antigens have been reported in a small proportion of RA patients (reviewed in [ 7 ]), and more recently autoantibodies to deiminated 'citrullinated' peptides have been described, suggesting that they may be important autoantigens in this disease. (
  • Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. (
  • Some patients with Noonan syndrome type 1 develop multiple giant cell lesions of the jaw or other bony or soft tissues, which are classified as pigmented villomoduolar synovitis (PVNS) when occurring in the jaw or joints. (
  • No other known p38 phosphatases were induced by dexamethasone, and other cell types which failed to express MKP-1 also failed to inhibit p38 in response to dexamethasone. (
  • One type of NK cell-mediated cytotoxicity is Ab-dependent cell-mediated cytotoxicity (ADCC), 3 in which Fc receptors on an NK cell recognize an Ab-coated target cell. (
  • Another type of NK cell-mediated cytotoxicity is initiated by direct MHC-nonrestricted recognition of target cells. (
  • Mast cell-derived IL-13 downregulates IL-12 production by skin dendritic cells to inhibit the TH1 cell response to cutaneous antigen exposure. (
  • Hematopoietic Stem Cell Transplantation Is a Curative Therapy for Transferrin Receptor 1 (TFRC) Deficiency. (
  • Many studies on SHP-1 revealed that the expression of this protein was diminished or abolished in several of the cancer cell lines and tissues examined. (
  • Here, the kinase activity is mostly switched on, contributing to the deregulation of cell growth. (
  • In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. (
  • We have previously reported that these approaches allowed us to identify several candidate proteins that are assumed to be involved in progressions of gastric cancer ( 12 ) and colon cancer ( 13 ) and have validated these approaches for discovery of biomarker by showing the role of aberrant glycosylation of protein tyrosine phosphatase κas an example in cancer cell migration ( 13 ). (
  • Immunologic reconstitution following hematopoietic stem cell transplantation despite lymph node paucity in NF-?B-inducing kinase deficiency. (
  • Efficient phosphorylation of the FcεRI requires specialized regions of the cell membrane that are enriched in cholesterol and sphingolipids (commonly termed lipid rafts) as both Lyn and FcεRI can be concentrated in these domains upon receptor engagement ( 3 ). (
  • The Den Hertog group studies the function of protein-tyrosine phosphatases in development and disease, using biochemical and cell biological approaches. (
  • Thus, Ras proteins are critical in stimulating cell growth and division. (
  • A kinase-independent function of AKT promotes cancer cell survival. (
  • Patients typically have recurrent infections and can vary with presentation and complications depending upon where the defect has occurred in B-cell development or the degree of functional impairment. (
  • By generating cell lines that inducibly express either wild-type or mutated forms of MCG10 and MCG10as, we found that MCG10 and MCG10as can suppress cell proliferation by inducing apoptosis and cell cycle arrest in G 2 -M. In addition, we found that MCG10 and MCG10as, through their KH domains, can bind poly(C) and that their RNA-binding activity is necessary for inducing apoptosis and cell cycle arrest. (
  • Some interactions are conserved, such as that between human HLA-E and the CD94:NKG2A receptor [7] , whereas others are highly variable, notably those between HLA-A, B, C and killer cell immunoglobulin-like receptors (KIR) [8] . (
  • The ability to migrate is a hallmark of various cell types and plays a crucial role in several physiological processes, including embryonic development, wound healing, and immune responses. (
  • Within the past years various cell migration assays have been developed to analyze the migratory behavior of different cell types. (
  • Various cell types could be analyzed using this technique, including lymphocytes/leukocytes, stem cells, and tumor cells. (
  • Coupling with G proteins , they are called seven-transmembrane receptors because they pass through the cell membrane seven times. (
  • Mice lacking IRS2 exhibit impaired suppression of hepatic glucose production ( 8 - 10 ) and β-cell failure ( 11 ), developing fasting hyperglycemia at 6-8 wks of age and severe type 2 diabetes at 10-12 wks of age ( 8 ). (
  • A promiscuous biotin ligase fusion protein identifies proximal and interacting proteins in mammalian cells. (
  • Mouse genetics experiments have defined crucial roles for each known mammalian STAT. The discovery of a STAT in Drosophila , and most recently in Dictyostelium discoideum , implies an ancient evolutionary origin for this dual-function set of proteins. (
  • The mammalian JAKs include four large tyrosine kinases (∼1200 amino acids) characterized by a COOH-located kinase and a neighboring domain that resembles but is not an active kinase. (
  • EGFR is amplified or overexpressed in a wide range of human cancers where it is thought to play an important role in tumor progression ( 12 ). (
  • However, the prognosis in patients with wild-type EGFR was improved with chemotherapy ( 7 ). (
  • However, a variety of treatment responses are observed and the sensitivity towards EGFR-TKIs diminished following 8-12 months of treatment ( 7 , 10 ). (
  • Scripts were written for reassembly of contiguous exons identified from genomic sequence to generate the predicted catalytic domain sequence of each kinase. (
  • βarrestin (βarr)-1 and -2 (βarrs) (or Arrestin-2 and -3, respectively) are universal G protein-coupled receptor (GPCR) adapter proteins expressed abundantly in extra-retinal tissues, including the myocardium. (
  • Defects in PTPN11 are the cause of LEOPARD syndrome type 1 (LEOPARD1) [MIM:151100]. (
  • Functional Shp2, encoded by ptpn11, is required for regeneration of zebrafish embryonic caudal fin-folds. (
  • The tumor-suppressing phosphatases operate at two levels. (
  • An aberrant glycosylation induced by N -acetylglucosaminyltransferase V (GnT-V), 1 is a representative example of such protein modification as is implicated in tumor progression. (
  • We estimated odds ratios and 95% confidence intervals for associations between each candidate SNP and tumor mutation type in 279 individuals from a clinical trial of adjuvant imatinib mesylate. (
  • These results suggest that the MCG10 RNA-binding protein is a potential mediator of p53 tumor suppression. (