Src homology domains. Medical search

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 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.

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

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 broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes

The 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.

Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

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

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.

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.

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

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.

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

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.

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.

The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.

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

Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.

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.

Established cell cultures that have the potential to propagate indefinitely.

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

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.

Proteins prepared by recombinant DNA technology.

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.

The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.

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.

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.

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

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).

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

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).)

Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.

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

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.

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.

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).

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.

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.

Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.

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.

Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.

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.

Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.

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.

The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.

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.

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.

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

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.

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.

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 class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.

A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.

A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.

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 phosphoinositide present in all eukaryotic cells, particularly in the plasma membrane. It is the major substrate for receptor-stimulated phosphoinositidase C, with the consequent formation of inositol 1,4,5-triphosphate and diacylglycerol, and probably also for receptor-stimulated inositol phospholipid 3-kinase. (Kendrew, The Encyclopedia of Molecular Biology, 1994)

A family of high molecular weight GTP phosphohydrolases that play a direct role in vesicle transport. They associate with microtubule bundles (MICROTUBULES) and are believed to produce mechanical force via a process linked to GTP hydrolysis. This enzyme was formerly listed as EC 3.6.1.50.

The degree of similarity between sequences. Studies of AMINO ACID SEQUENCE HOMOLOGY and NUCLEIC ACID SEQUENCE HOMOLOGY provide useful information about the genetic relatedness of genes, gene products, and species.

The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN.

Monomeric subunits of primarily globular ACTIN and found in the cytoplasmic matrix of almost all cells. They are often associated with microtubules and may play a role in cytoskeletal function and/or mediate movement of the cell or the organelles within the cell.

A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC 3.1.4.3), it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.

A 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.

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.

Deletion of sequences of nucleic acids from the genetic material of an individual.

The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)

Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.

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.

Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.

Proteins that activate the GTPase of specific GTP-BINDING PROTEINS.

The process by which two molecules of the same chemical composition form a condensation product or polymer.

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

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

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)

Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. c-crk protein is closely related to ONCOGENE PROTEIN V-CRK and includes several alternatively spliced isoforms.

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.

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

The rate dynamics in chemical or physical systems.

Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.

A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.

Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.

A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.

The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.

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.

Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.

Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.

A 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.

Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.

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.

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.

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).

A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.

A subtype of dynamin found primarily in the NEURONS of the brain.

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

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.

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.

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.

Signaling proteins which function as master molecular switches by activating Rho GTPases through conversion of guanine nucleotides. Rho GTPases in turn control many aspects of cell behavior through the regulation of multiple downstream signal transduction pathways.

Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to the hexahydroxy alcohol, myo-inositol. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid, myo-inositol, and 2 moles of fatty acids.

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)

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.

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.

Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.

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.

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.

Enzymes that hydrolyze GTP to GDP. EC 3.6.1.-.

Proteins found in any species of bacterium.

A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.

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

A member of the Rho family of MONOMERIC GTP-BINDING PROTEINS. It is associated with a diverse array of cellular functions including cytoskeletal changes, filopodia formation and transport through the GOLGI APPARATUS. This enzyme was formerly listed as EC 3.6.1.47.

PROTEINS that specifically activate the GTP-phosphohydrolase activity of RAS PROTEINS.

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

The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.

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.

Retroviral proteins that have the ability to transform cells. They can induce sarcomas, leukemias, lymphomas, and mammary carcinomas. Not all retroviral proteins are oncogenic.

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.

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

NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.

A signal transducing adaptor protein that is encoded by the crk ONCOGENE from TYPE C AVIAN RETROVIRUSES. It contains SRC HOMOLOGY DOMAINS and is closely related to its cellular homolog, PROTO-ONCOGENE PROTEIN C-CRK.

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 large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.

Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).

Protein analogs and derivatives of the Aequorea victoria green fluorescent protein that emit light (FLUORESCENCE) when excited with ULTRAVIOLET RAYS. They are used in REPORTER GENES in doing GENETIC TECHNIQUES. Numerous mutants have been made to emit other colors or be sensitive to pH.

Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.

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

Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.

The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.

A broad category of proteins involved in the formation, transport and dissolution of TRANSPORT VESICLES. They play a role in the intracellular transport of molecules contained within membrane vesicles. Vesicular transport proteins are distinguished from MEMBRANE TRANSPORT PROTEINS, which move molecules across membranes, by the mode in which the molecules are transported.

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

A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.

Any 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.

Proteins which are involved in the phenomenon of light emission in living systems. Included are the "enzymatic" and "non-enzymatic" types of system with or without the presence of oxygen or co-factors.

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

Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.

Protein interaction domains of about 70-90 amino acid residues, named after a common structure found in PSD-95, Discs Large, and Zona Occludens 1 proteins. PDZ domains are involved in the recruitment and interaction of proteins, and aid the formation of protein scaffolds and signaling networks. This is achieved by sequence-specific binding between a PDZ domain in one protein and a PDZ motif in another protein.

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.

Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.

The relationships of groups of organisms as reflected by their genetic makeup.

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

Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.

Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.

The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).

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.

Proto-oncogene proteins that negatively regulate RECEPTOR PROTEIN-TYROSINE KINASE signaling. It is a UBIQUITIN-PROTEIN LIGASE and the cellular homologue of ONCOGENE PROTEIN V-CBL.

A continuous cell line of high contact-inhibition established from NIH Swiss mouse embryo cultures. The cells are useful for DNA transfection and transformation studies. (From ATCC [Internet]. Virginia: American Type Culture Collection; c2002 [cited 2002 Sept 26]. Available from http://www.atcc.org/)

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 set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)

A high molecular weight (220-250 kDa) water-soluble protein which can be extracted from erythrocyte ghosts in low ionic strength buffers. The protein contains no lipids or carbohydrates, is the predominant species of peripheral erythrocyte membrane proteins, and exists as a fibrous coating on the inner, cytoplasmic surface of the membrane.

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.

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

Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.

The sum of the weight of all the atoms in a molecule.

A mammalian homolog of the DROSOPHILA SON OF SEVENLESS PROTEIN. It is a guanine nucleotide exchange factor for RAS PROTEINS.

Proteins found in any species of fungus.

A binding partner for several RECEPTOR PROTEIN-TYROSINE KINASES, including INSULIN RECEPTOR and INSULIN-LIKE GROWTH FACTOR RECEPTOR. It contains a C-terminal SH2 DOMAIN and mediates various SIGNAL TRANSDUCTION pathways.

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.

A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.

Glycoproteins found on the membrane or surface of cells.

A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).

A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.

A subclass of myosins found generally associated with actin-rich membrane structures such as filopodia. Members of the myosin type I family are ubiquitously expressed in eukaryotes. The heavy chains of myosin type I lack coiled-coil forming sequences in their tails and therefore do not dimerize.

Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.

Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.

Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.

Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)

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 genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.

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

Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)

A cell line derived from cultured tumor cells.

Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.

A rac GTP-binding protein involved in regulating actin filaments at the plasma membrane. It controls the development of filopodia and lamellipodia in cells and thereby influences cellular motility and adhesion. It is also involved in activation of NADPH OXIDASE. This enzyme was formerly listed as EC 3.6.1.47.

Structures which are part of the CELL MEMBRANE or have cell membrane as a major part of their structure.

Adherence of cells to surfaces or to other cells.

A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.

Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.

A process whereby multiple RNA transcripts are generated from a single gene. Alternative splicing involves the splicing together of other possible sets of EXONS during the processing of some, but not all, transcripts of the gene. Thus a particular exon may be connected to any one of several alternative exons to form a mature RNA. The alternative forms of mature MESSENGER RNA produce PROTEIN ISOFORMS in which one part of the isoforms is common while the other parts are different.

Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.

A microfilament protein that interacts with F-ACTIN and regulates cortical actin assembly and organization. It is also an SH3 DOMAIN containing phosphoprotein, and it mediates tyrosine PHOSPHORYLATION based SIGNAL TRANSDUCTION by PROTO-ONCOGENE PROTEIN PP60(C-SRC).

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.

Catalyzes the ATP-dependent PHOSPHORYLATION of GMP to generate GDP and ADP.

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

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.

MONOMERIC GTP-BINDING PROTEINS that were initially recognized as allosteric activators of the MONO(ADP-RIBOSE) TRANSFERASE of the CHOLERA TOXIN catalytic subunit. They are involved in vesicle trafficking and activation of PHOSPHOLIPASE D. This enzyme was formerly listed as EC 3.6.1.47

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.

A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.

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

Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.

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

A light microscopic technique in which only a small spot is illuminated and observed at a time. An image is constructed through point-by-point scanning of the field in this manner. Light sources may be conventional or laser, and fluorescence or transmitted observations are possible.

Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.

A sub-family of RHO GTP-BINDING PROTEINS that is involved in regulating the organization of cytoskeletal filaments. This enzyme was formerly listed as EC 3.6.1.47.

Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. (1/3051)

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

Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation. (2/3051)

We have identified Socs1 as a downstream component of the Kit receptor tyrosine kinase signalling pathway. We show that the expression of Socs1 mRNA is rapidly increased in primary bone marrow-derived mast cells following exposure to Steel factor, and Socs1 inducibly binds to the Kit receptor tyrosine kinase via its Src homology 2 (SH2) domain. Previous studies have shown that Socs1 suppresses cytokine-mediated differentiation in M1 cells inhibiting Janus family kinases. In contrast, constitutive expression of Socs1 suppresses the mitogenic potential of Kit while maintaining Steel factor-dependent cell survival signals. Unlike Janus kinases, Socs1 does not inhibit the catalytic activity of the Kit tyrosine kinase. In order to define the mechanism by which Socs1-mediated suppression of Kit-dependent mitogenesis occurs, we demonstrate that Socs1 binds to the signalling proteins Grb-2 and the Rho-family guanine nucleotide exchange factors Vav. We show that Grb2 binds Socs1 via its SH3 domains to putative diproline determinants located in the N-terminus of Socs1, and Socs1 binds to the N-terminal regulatory region of Vav. These data suggest that Socs1 is an inducible switch which modulates proliferative signals in favour of cell survival signals and functions as an adaptor protein in receptor tyrosine kinase signalling pathways. (+info)

Anopheles gambiae Ag-STAT, a new insect member of the STAT family, is activated in response to bacterial infection. (3/3051)

A new insect member of the STAT family of transcription factors (Ag-STAT) has been cloned from the human malaria vector Anopheles gambiae. The domain involved in DNA interaction and the SH2 domain are well conserved. Ag-STAT is most similar to Drosophila D-STAT and to vertebrate STATs 5 and 6, constituting a proposed ancient class A of the STAT family. The mRNA is expressed at all developmental stages, and the protein is present in hemocytes, pericardial cells, midgut, skeletal muscle and fat body cells. There is no evidence of transcriptional activation following bacterial challenge. However, bacterial challenge results in nuclear translocation of Ag-STAT protein in fat body cells and induction of DNA-binding activity that recognizes a STAT target site. In vitro treatment with pervanadate (vanadate and H2O2) translocates Ag-STAT to the nucleus in midgut epithelial cells. This is the first evidence of direct participation of the STAT pathway in immune responses in insects. (+info)

DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines. (4/3051)

The Src homology 3 (SH3) motif is found in numerous signal transduction proteins involved in cellular growth and differentiation. We have purified and cloned a novel protein, DEF-1 (differentiation-enhancing factor), from bovine brain by using a Src SH3 affinity column. Ectopic expression of DEF-1 in fibroblasts resulted in the differentiation of a significant fraction of the culture into adipocytes. This phenotype appears to be related to the induction of the transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma), since DEF-1 NIH 3T3 cells demonstrated augmented levels of PPARgamma mRNA and, when treated with activating PPARgamma ligands, efficient induction of differentiation. Further evidence for a role for DEF-1 in adipogenesis was provided by heightened expression of DEF-1 mRNA in adipose tissue isolated from obese and diabetes mice compared to that in tissue isolated from wild-type mice. However, DEF-1 mRNA was detected in multiple tissues, suggesting that the signal transduction pathway(s) in which DEF-1 is involved is not limited to adipogenesis. These results suggest that DEF-1 is an important component of a signal transduction process that is involved in the differentiation of fibroblasts and possibly of other types of cells. (+info)

Identification of a new Pyk2 target protein with Arf-GAP activity. (5/3051)

Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled receptors and by extracellular signals that elevate intracellular Ca2+ concentration. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells. Immunofluorescence experiments demonstrate that Pap is localized in the Golgi apparatus and at the plasma membrane, where it is colocalized with Pyk2. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Addition of recombinant Pap protein to Golgi preparations prevented Arf-dependent generation of post-Golgi vesicles in vitro. Moreover, overexpression of Pap in cultured cells reduced the constitutive secretion of a marker protein. We propose that Pap functions as a GAP for Arf and that Pyk2 may be involved in regulation of vesicular transport through its interaction with Pap. (+info)

Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Involvement of Jak2 in the stimulation of phosphatidylinositol 3-kinase. (6/3051)

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

C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor. (7/3051)

Increased expression of the insulin-like growth factor-I receptor (IGF-IR) protein-tyrosine kinase occurs in several kinds of cancer and induces neoplastic transformation in fibroblast cell lines. The transformed phenotype can be reversed by interfering with the function of the IGF-IR. The IGF-IR is required for transformation by a number of viral and cellular oncoproteins, including SV40 large T antigen, Ras, Raf, and Src. The IGF-IR is a substrate for Src in vitro and is phosphorylated in v-Src-transformed cells. We observed that the IGF-IR and IR associated with the C-terminal Src kinase (CSK) following ligand stimulation. We found that the SH2 domain of CSK binds to the tyrosine-phosphorylated form of IGF-IR and IR. We determined the tyrosine residues in the IGF-IR and in the IR responsible for this interaction. We also observed that fibroblasts stimulated with IGF-I or insulin showed a rapid and transient decrease in c-Src tyrosine kinase activity. The results suggest that c-Src and CSK are involved in IGF-IR and IR signaling and that the interaction of CSK with the IGF-IR may play a role in the decrease in c-Src activity following IGF-I stimulation. (+info)

Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. (8/3051)

Adapter proteins made up of Src homology (SH) domains mediate multiple cellular signaling events initiated by receptor protein tyrosine kinases. Here we report that Grb4 is an adapter protein closely related to but distinct from Nck that is made up of three SH3 domains and one SH2 domain. Northern analysis indicated that both genes are expressed in multiple tissues. Both Nck and Grb4 proteins could associate with receptor tyrosine kinases and the SH3-binding proteins PAK, Sos1, and PRK2, and they synergized with v-Abl and Sos to induce gene expression via the transcription factor Elk-1. Although neither protein was transforming on its own, both Nck and Grb4 cooperated with v-Abl to transform NIH 3T3 cells and influenced the morphology and anchorage-dependent growth of wild type Ras-transformed cells. Nck and Grb4 therefore appear to be functionally redundant. (+info)

Homologs of both the Src homology 2 and Src homology 3 domains are found in numerous other proteins. The Src homology 1 domain ... In biology, a Src homology domain is one of the two small protein binding domains found in the Src oncoprotein. ... In terms of initiating the cell cycle when growth factor signals are present, "Src homology domains" are found on Grb2 proteins ... v t e v t e (All stub articles, Protein stubs, Cell biology stubs, Protein domains). ...

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

... is a protein that in humans is encoded by the SHF gene. GRCh38: Ensembl release 89: ... "Entrez Gene: Src homology 2 domain containing F". Retrieved 2018-05-27. v t e (Genes on human chromosome 15, All stub articles ...

https://en.wikipedia.org/wiki/Src_homology_2_domain_containing_f

Musacchio, A; Noble, M; Pauptit, R; Wierenga, R; Saraste, M (Oct 29, 1992). "Crystal structure of a Src-homology 3 (SH3) domain ... "Structure of the pleckstrin homology domain from beta-spectrin". Nature. 369 (6482): 675-7. Bibcode:1994Natur.369..675M. doi: ... contributing to the determination of the first crystallographic structures of the SH3 and PH domains. During his post-doctoral ... "Modular assembly of RWD domains on the Mis12 complex underlies outer kinetochore organization". Molecular Cell. 53 (4): 591-605 ...

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

... possible involvement of Src homology 2 domains". J. Cereb. Blood Flow Metab. 19 (8): 880-8. doi:10.1097/00004647-199908000- ... "The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases". J. Biol. Chem. 276 (20): 17199-205. ... "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. 271 (41): 25646-56. doi:10.1074/jbc.271.41.25646. PMID ... "Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains". Mol. Cell. Biol. 15 (10): 5725 ...

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

"Identification of Itk/Tsk Src homology 3 domain ligands". The Journal of Biological Chemistry. 271 (41): 25646-56. doi:10.1074/ ... RNA binding protein domains in other proteins that are similar to the RNA binding domain of protein K are called K-homology or ... July 1994). "Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains". Molecular ... The protein encoded by this gene is located in the nucleoplasm and has three repeats of KH domains that binds to RNAs. It is ...

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

Src homology 3) SH2 - (Src homology 2) C-terminus - tyrosine kinase, catalytic domain ITK (gene) has been shown to interact ... pleckstrin homology domain) TH - Tec family homology domain (including Bruton's tyrosine kinase Cys-rich motif and Proline rich ... Shim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR (2004). "Association of the Src homology 2 domain-containing leukocyte ... Bunnell SC, Henry PA, Kolluri R, Kirchhausen T, Rickles RJ, Berg LJ (1996). "Identification of Itk/Tsk Src homology 3 domain ...

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

"Identification of Itk/Tsk Src homology 3 domain ligands". The Journal of Biological Chemistry. 271 (41): 25646-56. doi:10.1074/ ... "Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains". Molecular and Cellular Biology ... a C-terminal VCA domain and central B and GBD (GTP binding domain) domains. WASp, is expressed exclusively in hematopoietic ... WAML (WASP and MIM like), WAWH (WASP without WH1 domain), and WHIMP (WAVE Homology in Membrane Protrusions) have more recently ...

https://en.wikipedia.org/wiki/Wiskott–Aldrich_syndrome_protein

1996). "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. 271 (41): 25646-56. doi:10.1074/jbc.271.41. ... 1994). "Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains". Mol. Cell. Biol ... Sam68 (the Src-Associated substrate in Mitosis of 68 kDa) is officially called KHDRBS1 (KH domain containing, RNA binding, ... This gene encodes a member of the K homology domain-containing, RNA-binding, signal transduction-associated protein family. The ...

https://en.wikipedia.org/wiki/KHDRBS1

"Phosphopeptide selective coordination complexes as promising SRC homology 2 domain mimetics." Inorganic Chemistry. 2012 Aug 6; ... "Progress towards the development of SH2 domain inhibitors." Chemical Society Review. 2013 Apr 21;42(8):3337-70. Drewry JA, ...

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

The SH2 (Src Homology 2) domain is a structurally conserved protein domain contained within the Src oncoprotein and in many ... SH2 domains allow proteins containing those domains to dock to phosphorylated tyrosine residues on other proteins. SH2 domains ... One of the more prominent domains is the SH2 domain. SH2 domains play a vital role in cellular communication. Its length is ... "Defining the specificity space of the human SRC homology 2 domain". Molecular & Cellular Proteomics. 7 (4): 768-84. doi:10.1074 ...

https://en.wikipedia.org/wiki/SH2_domain

Calponin homology (CH) domain, which is an F-actin binding motif; Src homology 2 (SH2) domain, which mediate interaction with ... Protein domains enriched in the adhesome include: Pleckstrin homology (PH) and FERM domains, which target proteins to the ... examined the effect of inhibition of myosin contractility on the integrin adhesome composition and found LIM domain proteins ... The adhesome contains multi domain proteins with various functions, some of which are specifically enriched in the adhesome ...

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

This gene encodes a protein with src homology domain 3 (SH3) patterns. Mutations in this gene cause familial juvenile ... "A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile ... Donaldson JC, Dise RS, Ritchie MD, Hanks SK (Aug 2002). "Nephrocystin-conserved domains involved in targeting to epithelial ... Donaldson JC, Dise RS, Ritchie MD, Hanks SK (Aug 2002). "Nephrocystin-conserved domains involved in targeting to epithelial ...

https://en.wikipedia.org/wiki/NPHP1

"Specificity of the binding of synapsin I to Src homology 3 domains". The Journal of Biological Chemistry. 275 (38): 29857-67. ... a middle clathrin and adaptor binding domain and a C-terminal SH3 domain. In the brain, its primary function is thought to be ... "The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding ... "The SH3 domain of amphiphysin binds the proline-rich domain of dynamin at a single site that defines a new SH3 binding ...

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

Ye ZS, Baltimore D (1995). "Binding of Vav to Grb2 through dimerization of Src homology 3 domains". Proc. Natl. Acad. Sci. U.S. ... Ye ZS, Baltimore D (Dec 1994). "Binding of Vav to Grb2 through dimerization of Src homology 3 domains". Proc. Natl. Acad. Sci. ... "Interleukin 3 and erythropoietin induce association of Vav with Tec kinase through Tec homology domain". Oncogene. 11 (4): 619- ... Katzav S, Cleveland JL, Heslop HE, Pulido D (1991). "Loss of the amino-terminal helix-loop-helix domain of the vav proto- ...

https://en.wikipedia.org/wiki/VAV1

"Entrez Gene: SHC3 SHC (Src homology 2 domain containing) transforming protein 3". Nakamura T, Komiya M, Sone K, Hirose E, Gotoh ... "A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is ... Miyake I, Hakomori Y, Misu Y, Nakadate H, Matsuura N, Sakamoto M, Sakai R (April 2005). "Domain-specific function of ShcC ... Their differential regional expression in the brain and roles in neurotrophin and Src signaling". The Journal of Biological ...

https://en.wikipedia.org/wiki/SHC3

"Entrez Gene: SHC2 SHC (Src homology 2 domain containing) transforming protein 2". Warner, A J; Lopez-Dee J; Knight E L; ... Their differential regional expression in the brain and roles in neurotrophin and Src signaling". J Biol Chem. 273 (12): 6960-7 ... SHC2 has been shown to interact with Kinase insert domain receptor. GRCh38: Ensembl release 89: ENSG00000129946 - Ensembl, May ... Kavanaugh WM; Williams LT (Jan 1995). "An alternative to SH2 domains for binding tyrosine-phosphorylated proteins". Science. ...

https://en.wikipedia.org/wiki/SHC2

Zhang H, Gallo KA (2002). "Autoinhibition of mixed lineage kinase 3 through its Src homology 3 domain". J. Biol. Chem. 276 (49 ... a novel src-homology 3 domain-containing proline-rich kinase with serine/threonine kinase activity". J. Biol. Chem. 269 (21): ... identification of a widely-expressed protein kinase bearing an SH3 domain and a leucine zipper-basic region domain". Oncogene. ... This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and ...

https://en.wikipedia.org/wiki/MAP3K11

June 2001). "Molecular cloning and characterization of Bif-1. A novel Src homology 3 domain-containing protein that associates ... It has also been shown to interact with a wide variety of proteins through a canonical SH3 domain that enables PxxP motif- ... "Entrez Gene: SH3GLB1 SH3-domain GRB2-like endophilin B1". Takahashi Y, Coppola D, Matsushita N, Cualing HD, Sun M, Sato Y, et ... Masuda M, Takeda S, Sone M, Ohki T, Mori H, Kamioka Y, Mochizuki N (June 2006). "Endophilin BAR domain drives membrane ...

https://en.wikipedia.org/wiki/SH3GLB1

"5-Lipoxygenase contains a functional Src homology 3-binding motif that interacts with the Src homology 3 domain of Grb2 and ... Ye ZS, Baltimore D (December 1994). "Binding of Vav to Grb2 through dimerization of Src homology 3 domains". Proceedings of the ... Okkenhaug K, Rottapel R (August 1998). "Grb2 forms an inducible protein complex with CD28 through a Src homology 3 domain- ... Braverman LE, Quilliam LA (February 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter ...

https://en.wikipedia.org/wiki/GRB2

A novel Src homology 3 domain-containing protein that associates with Bax". J. Biol. Chem. 276 (23): 20559-65. doi:10.1074/jbc. ... Bcl-2 family members share one or more of the four characteristic domains of homology entitled the Bcl-2 homology (BH) domains ... These domains are composed of nine α-helices, with a hydrophobic α-helix core surrounded by amphipathic helices and a ... In the protein's inactive form, the groove binds its transmembrane domain, transitioning it from a membrane-bound to a ...

https://en.wikipedia.org/wiki/Bcl-2-associated_X_protein

Gigoux V, L'Hoste S, Raynaud F, Camonis J, Garbay C (2002). "Identification of Aurora kinases as RasGAP Src homology 3 domain- ... The family members have highly conserved C-terminal catalytic domains. Their N-terminal domains, however, exhibit a large ...

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

He identified the phosphotyrosine-binding Src homology 2 (SH2 domain) as the prototypic non-catalytic interaction module. SH2 ... Moran, M. F. (1990). "Src Homology Region 2 Domains Direct Protein-Protein Interactions in Signal Transduction". Proceedings of ... Since the discovery of SH2 domains, hundreds of different modules have been identified in many proteins. Born in Maidstone, ... Pawson, T.; Nash, P. (2003). "Assembly of Cell Regulatory Systems Through Protein Interaction Domains". Science. 300 (5618): ...

https://en.wikipedia.org/wiki/Tony_Pawson_(biochemist)

"Entrez Gene: SHB Src homology 2 domain containing adaptor protein B". Karlsson T, Songyang Z, Landgren E, Lavergne C, Di Fiore ... Lindholm CK, Gylfe E, Zhang W, Samelson LE, Welsh M (Sep 1999). "Requirement of the Src homology 2 domain protein Shb for T ... Lindholm CK, Gylfe E, Zhang W, Samelson LE, Welsh M (Sep 1999). "Requirement of the Src homology 2 domain protein Shb for T ... Karlsson T, Kullander K, Welsh M (Sep 1998). "The Src homology 2 domain protein Shb transmits basic fibroblast growth factor- ...

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

Leto TL, Adams AG, de Mendez I (1994). "Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline- ... "Specificity of the binding of synapsin I to Src homology 3 domains". J. Biol. Chem. 275 (38): 29857-67. doi:10.1074/jbc. ... Finan PM, Hall A, Kellie S (1996). "Sam68 from an immortalised B-cell line associates with a subset of SH3 domains". FEBS Lett ... bind to moesin through their PX domain". Biochem. Biophys. Res. Commun. 289 (2): 382-8. doi:10.1006/bbrc.2001.5982. PMID ...

https://en.wikipedia.org/wiki/Neutrophil_cytosolic_factor_1

It belongs to the adaptor-type Src homology (SH)2-containing molecules. Src homology 2 domains are globular protein modules ... binds to the Src homology 3 domains of CRK and GRB2/ASH proteins". Proceedings of the National Academy of Sciences of the ... sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk ... "Transformation suppressor activity of C3G is independent of its CDC25-homology domain". Oncogene. 16 (5): 613-24. doi:10.1038/ ...

https://en.wikipedia.org/wiki/RAPGEF1

Alexandropoulos K, Cheng G, Baltimore D (1995). "Proline-rich sequences that bind to Src homology 3 domains with individual ... This allows SRC or SRC family kinase to bind NEDD9 via its SH2 domain. Phosphorylation of the NEDD9 substrate domain by Src and ... "Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas)". J. ... which contains a Src homology 3 domain and associates with Fyn". Oncogene. 11 (11): 2331-8. PMID 8570184. ...

https://en.wikipedia.org/wiki/NEDD9

This gene encodes a Src homology 2 domain-binding protein 1-like protein. The encoded protein interacts with heat shock 70 kDa ... v t e This article incorporates text from the United States National Library of Medicine, which is in the public domain. ( ...

https://en.wikipedia.org/wiki/Shc_binding_and_spindle_associated_1_like

2002). "Identification of Aurora kinases as RasGAP Src homology 3 domain-binding proteins". J. Biol. Chem. 277 (26): 23742-6. ... This article incorporates text from the United States National Library of Medicine, which is in the public domain. Portal: ... Wordeman, L; Wagenbach, M; Maney, T (1999). "Mutations in the ATP-binding domain affect the subcellular distribution of mitotic ...

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

"Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains". Molecular and Cellular Biology ... of regions of the Wiskott-Aldrich syndrome protein responsible for association with selected Src homology 3 domains" (PDF). The ... a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine- ... This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein contains N-terminal sites for ...

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

Shim EK, Moon CS, Lee GY, Ha YJ, Chae SK, Lee JR (September 2004). "Association of the Src homology 2 domain-containing ... Braverman LE, Quilliam LA (February 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter ... "Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains". Mol. Cell. Biol. 15 (10): 5725 ... "Wiskott-Aldrich syndrome protein physically associates with Nck through Src homology 3 domains". Mol. Cell. Biol. 15 (10): 5725 ...

https://en.wikipedia.org/wiki/NCK1

Src homology 4 domain (SH4 domain), unique region, SH3 domain, SH2 domain, catalytic domain and short regulatory tail. When Src ... Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src (cellular Src; pronounced "sarc ... viral Src) gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript ... Thus, c-Src plays a key role in the tumor progression of breast cancers. Members of the Src family kinases Src, Lyn and Fgr are ...

https://en.wikipedia.org/wiki/Proto-oncogene_tyrosine-protein_kinase_Src

June 2011). "Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in ...

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

Wang B, Golemis EA, Kruh GD (July 1997). "ArgBP2, a multiple Src homology 3 domain-containing, Arg/Abl-interacting protein, is ... "Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association ... Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene ... Warmuth M, Bergmann M, Priess A, Häuslmann K, Emmerich B, Hallek M (December 1997). "The Src family kinase Hck interacts with ...

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

... and Src homology 2 domain-containing protein phosphatase 2 pathways to inhibit the actions of pro-inflammatory cytokines; c) ...

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

Through interactions with proteins containing SRC (MIM 190090) homology-2 (SH2) and SH3 domains, CBL proteins modulate ... 1999). "Activating SRC mutation in a subset of advanced human colon cancers". Nat. Genet. 21 (2): 187-90. doi:10.1038/5971. ... Loreto MP, Berry DM, McGlade CJ (2002). "Functional Cooperation between c-Cbl and Src-Like Adaptor Protein 2 in the Negative ... Kim M, Tezuka T, Tanaka K, Yamamoto T (2004). "Cbl-c suppresses v-Src-induced transformation through ubiquitin-dependent ...

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

Nedrelow JH, Cianci CD, Morrow JS (Feb 2003). "c-Src binds alpha II spectrin's Src homology 3 (SH3) domain and blocks calpain ... "Identification of a candidate human spectrin Src homology 3 domain-binding protein suggests a general mechanism of association ... Bennett PM, Maggs AM, Baines AJ, Pinder JC (Apr 2006). "The transitional junction: a new functional subcellular domain at the ... Hirai H, Matsuda S (September 1999). "Interaction of the C-terminal domain of delta glutamate receptor with spectrin in the ...

https://en.wikipedia.org/wiki/SPTAN1

This protein has several SH2 and SH3 domains (src-homology domains) and is involved in several signaling pathways, recruiting ... 1995). "v-Crk modulation of growth factor-induced PC12 cell differentiation involves the Src homology 2 domain of v-Crk and ... 1994). "C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2 ... Crk should not be confused with Src, which also has cellular (c-Src) and viral (v-Src) forms and is involved in some of the ...

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

Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1) is an enzyme with phosphatase activity. ... Lamkin TD, Walk SF, Liu L, Damen JE, Krystal G, Ravichandran KS (April 1997). "Shc interaction with Src homology 2 domain ... Zhang J, Walk SF, Ravichandran KS, Garrison JC (July 2009). "Regulation of the Src homology 2 domain-containing inositol 5'- ... March ME, Lucas DM, Aman MJ, Ravichandran KS (September 2000). "p135 src homology 2 domain-containing inositol 5'-phosphatase ( ...

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

... src gene - src-family kinase - SSRI - starch - stem cell - stereochemistry - steroid 17alpha-monooxygenase - steroid 21- ... catalytic domain - CCR5 receptor - CD4 antigen - CD45 antigen - CD95 antigen - CDC28 protein kinase - cell - cell adhesion ... amino acid sequence homology - aminobutyric acid - ammonia - AMPA receptor - amyloid - anabolism - anaerobic respiration - ... SH3 domain - SI - sigma factor - signal peptide - signal recognition particle - signal sequence - signal transduction - ...

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

Other domains, such as PDZ (postsynaptic density protein-95, discs-large, zona occludens-1), SH3 (Src homology 3) and RA (Ras- ... A homology domain with yeast's PX domain is localized between amino acids 75 and 178 within this same domain. As it is a ... As a protein of the SNXs family, the SNX8 is formed of 465 aminoacids and presents a BAR-domain and a PX-domain which are very ... The SNX-BAR proteins that contain both domains are a part of phosphoinositide-enriched, high-curvature tubular micro-domains of ...

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

"Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by ... Vadlamudi RK, Joung I, Strominger JL, Shin J (1996). "p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, ... "Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain". Proc Natl Acad Sci U S A. 93 (12): 5991-5 ... "Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget's disease of bone". ...

https://en.wikipedia.org/wiki/Sequestosome_1

Jia CY, Nie J, Wu C, Li C, Li SS (Aug 2005). "Novel Src homology 3 domain-binding motifs identified from proteomic screen of a ... NCBI identifies a protein domain of unknown function between amino acids Asp435 and Leu671, known as DUF1741 (Domain of Unknown ... specifically via the SH3 protein binding domain. The potential SH3-binding domain exists within a low complexity region with an ... ARMH3 or Armadillo Like Helical Domain Containing 3, also known as UPF0668 and c10orf76, is a protein that in humans is encoded ...

https://en.wikipedia.org/wiki/ARMH3

... are critical for binding of Src-homology 2 domain-containing kinases such as spleen tyrosine kinase (Syk) and signal ... a single span transmembrane region and a short cytoplasmic domain. The cytoplasmic domain contains multiple phosphorylation ... The CD79a cytoplasmic domain further contains a non-ITAM tyrosine distal of the CD79a ITAM (human CD79a Tyr210, mouse CD79a ... This article incorporates text from the United States National Library of Medicine, which is in the public domain. (Articles ...

https://en.wikipedia.org/wiki/CD79A

The cytoplasmic domains do not contain any intrinsic tyrosine kinase activity. Tyrosine residues of NTRs mostly appear in ... Members of a class have a high sequence homology and typically share the same gene locus. NTRs are transmembrane glycoproteins ... Phosphorylation of the tyrosine residues is performed by membrane-anchored Src family kinases (SFK) (e.g. Lck, Fyn, Lyn, Blk), ... These transmembrane receptors are not grouped into the NTR family based on sequence homology, but because they share a ...

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

This domain also aids in the binding of the central DNA-binding domain (DBD) to specific DNA sequences; the CTD is a positive ... 3) E4orf4 may use oncogenes that have been activated in cancer cells, including Src, to cause cell death. 4) Cancer cells have ... The name ORCTL3 was decided upon because of its structural homology to proteins belonging to the family of organic cation ... Conserved domains among human, mouse, and rat homologs include the leucine zipper (LZ) domain at the C-terminal region, two ...

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

"The role of the Src homology 3-Src homology 2 interface in the regulation of Src kinases". The Journal of Biological Chemistry ... Two of these domains, the N-terminal FERM domain and the Kinase domain form an auto-inhibitory interaction. This interaction- ... The amino-terminal domains of FAK share a significant sequence similarity with the band 4.1 domain first identified in ... "Tyrosine phosphorylation of focal adhesion kinase at sites in the catalytic domain regulates kinase activity: a role for Src ...

https://en.wikipedia.org/wiki/PTK2

... the Src homology domain-containing transforming protein 1 (SHC1), before being able to recruit SH2 domain-containing molecules ... It acts as a docking station for the Src homology 2(SH2) domain that is contained in the adaptor protein families Crk, Grb2, ... Adjacent to the PH domain is a central, proline-rich domain that contains many PXXP motifs for binding to the SH3 domains of ... Zhao C, Yu DH, Shen R, Feng GS (July 1999). "Gab2, a new pleckstrin homology domain-containing adapter protein, acts to ...

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

... and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the ... Each isometric monomer is structurally organized into 8 distinct domains consists of; a leucine-rich repeat domain (L1, ... Src Homology 2 - B ), APS and protein phosphatases, such as PTP1B, eventually promoting downstream processes involving blood ... "Insulin receptor kinase phosphorylates protein tyrosine phosphatase containing Src homology 2 regions and modulates its PTPase ...

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

Plenty of Src-homology-3 (POSH) has also been shown to be a partner of JIP1/2. All these JNK pathway regulators assemble ... A special extension to the C-terminal kinase domain core, the so-called "Domain for Versatile Docking" (DVD) is a region found ... These special MAPKK:MAPKKK kinase-domain/kinase-domain interactions facilitate the phosphorylation of MKK7. In addition to the ... that adds onto the back side of the catalytic core of the MAP2K kinase domains. This domain extension is both required for the ...

https://en.wikipedia.org/wiki/MAP2K7

"A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell ... "A novel Src homology 2 domain-containing molecule, Src-like adapter protein-2 (SLAP-2), which negatively regulates T cell ... Src-like-adapter 2 is a protein that in humans is encoded by the SLA2 gene. This gene encodes a member of the SLAP family of ... "Entrez Gene: SLA2 Src-like-adaptor 2". Pandey A, Ibarrola N, Kratchmarova I, Fernandez MM, Constantinescu SN, Ohara O, ...

https://en.wikipedia.org/wiki/SLA2

"A mammalian adaptor protein with conserved Src homology 2 and phosphotyrosine-binding domains is related to Shc and is ... a novel C1 domain-containing protein with homology to tensin". Biochemical and Biophysical Research Communications. 299 (5): ... Proteolytic cleavage of the AXL extracellular domain by the metalloproteinases ADAM10 and ADAM17 can downregulate this ... a member of the superfamily of G domain-containing proteins, as a ligand for Rse and Axl". The Journal of Biological Chemistry ...

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

Because of the high degree of homology in interaction domains and some identified common partners, CASS4 is likely to share ... this motif is conserved among the other three CAS family proteins and is an important binding site for the Src SH2 domain. ... domain. For the better studied members of the CAS family (BCAR1 and NEDD9), all of these domains have been defined as crucial ... Amino acid sequence homology of this isoform of human CASS4 with other family members is 26% overall identity and 42% ...

https://en.wikipedia.org/wiki/CASS4

1999). "Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in ... "Tyrosine phosphorylation of tub and its association with Src homology 2 domain-containing proteins implicate tub in ...

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

Leto TL, Adams AG, de Mendez I (1994). "Assembly of the phagocyte NADPH oxidase: binding of Src homology 3 domains to proline- ... a third cytosolic component of the activation complex of the NADPH oxidase to contain src homology 3 domains". Biochem. J. 296 ... The PX domain of this protein can bind phospholipid products of the PI(3) kinase, which suggests its role in PI(3) kinase- ... down-regulates NADPH oxidase activity through interactions with its SH3 domain". J. Biol. Chem. 272 (14): 9141-6. doi:10.1074/ ...

https://en.wikipedia.org/wiki/Neutrophil_cytosolic_factor_4

Braverman LE, Quilliam LA (February 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter ... a single membrane-spanning helix domain, an intracellular juxtamembrane domain, a split tyrosine kinase domain and a carboxylic ... "WDR48 WD repeat domain 48 [Homo sapiens (human)] - Gene - NCBI". "PRKG2 protein kinase cGMP-dependent 2 [Homo sapiens (human ... Li W, Hu P, Skolnik EY, Ullrich A, Schlessinger J (December 1992). "The SH2 and SH3 domain-containing Nck protein is oncogenic ...

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

Docking protein 1 contains a putative pleckstrin homology domain at the amino terminus and ten PXXP SH3 recognition motifs. ... Liang X, Wisniewski D, Strife A, Clarkson B, Resh MD (April 2002). "Phosphatidylinositol 3-kinase and Src family kinases are ... Songyang Z, Yamanashi Y, Liu D, Baltimore D (2001). "Domain-dependent function of the rasGAP-binding protein p62Dok in cell ...

https://en.wikipedia.org/wiki/DOK1

Conserved Domains (1) summary. cd10391. Location:393 → 490. SH2_SHE; Src homology 2 domain found in SH2 domain-containing ... Conserved Domains (1) summary. cd10391. Location:393 → 490. SH2_SHE; Src homology 2 domain found in SH2 domain-containing ... Conserved Domains (1) summary. cl15255. Location:393 → 434. SH2; Src homology 2 (SH2) domain. ... Src homology 2 domain containing Eprovided by HGNC. Primary source. HGNC:HGNC:27004 See related. Ensembl:ENSG00000169291 MIM: ...

https://www.ncbi.nlm.nih.gov/gene/126669

Copy number loss of (src homology 2 domain containing)-transforming protein 2 (SHC2) gene: discordant loss in monozygotic twins ... Src homology 2 domain containing)-transforming protein 2 (SHC2) gene in the distal 350-kb subtelomeric region of 19p13.3 in the ...

https://pubmed.ncbi.nlm.nih.gov/21658278/

P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase complexed to a peptide derived ... P395S mutant of the p85 regulatory subunit of the N-terminal src homology 2 domain of PI3-Kinase complexed to a peptide derived ... Previous genetic analysis has characterized mutants of the N-terminal src homology 2 (SH2) domain of the p85 subunit of ... Previous genetic analysis has characterized mutants of the N-terminal src homology 2 (SH2) domain of the p85 subunit of ...

https://www.rcsb.org/structure/1oo4

... domains, is involved in cell polarization. A Rho-type GTPase, Rho3p, is involved in the mai ... Yeast src homology region 3 domain-binding proteins involved in bud formation. Y Matsui, Y Matsui ... Y Matsui, R Matsui, R Akada, A Toh-e; Yeast src homology region 3 domain-binding proteins involved in bud formation.. J Cell ... The yeast protein Bem1p, which bears two src homology region 3 (SH3) domains, is involved in cell polarization. A Rho-type ...

https://rupress.org/jcb/article/133/4/865/15278/Yeast-src-homology-region-3-domain-binding

Direct Phosphorylation of SRC Homology 3 Domains by Tyrosine Kinase Receptors Disassembles Ligand-Induced Signaling Networks ... EPH receptors; SRC homology domain; adaptor proteins; protein interaction networks; proteomics; signal transduction; tyrosine ... Direct Phosphorylation of SRC Homology 3 Domains by Tyrosine Kinase Receptors Disassembles Ligand-Induced Signaling Networks ... terminate downstream signaling via the direct phosphorylation of an evolutionarily conserved Tyr present in most SRC homology ( ...

https://espace.inrs.ca/id/eprint/7433/

src Homology Domains. 1. 2014. 374. 0.030. Why? Kinetics. 1. 2021. 6921. 0.030. Why? ...

https://connects.catalyst.harvard.edu/Profiles/display/Person/154084/Network/ResearchAreas/details

The gap junction protein connexin32 interacts with the Src homology 3/hook domain of discs large homolog 1. J Biol Chem. 2007 ...

https://www.texaschildrens.org/find-a-doctor/ionela-iacobas-md

Intersectin, a novel adaptor protein with two Eps15 homology and five Src homology 3 domains. J. Biol. Chem. 273, 31401-31407 ( ...

https://www.nature.com/articles/s41588-022-01148-2?error=cookies_not_supported

SHC (Src homology 2 domain containing) transforming protein 2. MGI:106180 Go Annotations as Summary Text (Tabular View) (GO ... Homology: IAS. Inferred from ancestral sequence. IBA. Inferred from biological aspect of ancestor. IBD. Inferred from ...

http://www.informatics.jax.org/go/marker/MGI:106180

High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. Proc Natl ... 4] The genetic defect appears to be a region of the gene encoding the KRT14 nonhelical head (E1/V1) domain located between the ... The synthesis of short serine-rich peptides arising from the K14 head domain could impair its assembly. ... associated death domain protein (TRADD). Specifically, decreased KRT14 has been shown to lead to increased TNF-alpha-induced ...

http://emedicine.medscape.com/article/1117926-overview

Src homology domain-mediated protein interactions (January 21st, 2010). Hanna Lindfors. Application of fragment-based drug ... The BRCT domain from the large subunit of human Replication Factor C: Protein-DNA complex determined by NMR and mutagenesis ( ...

https://www.universiteitleiden.nl/en/science/chemistry/macbio/research/phd-theses

Description: Apo structure of the Grb7 SH2 domain. Class: signaling protein. Keywords: src Homology Domain, phosphotyrosine ... expression tag (1) Domains in SCOPe 2.08: d4wwqb1, d4wwqb2*Heterogens: MLA, HOH PDB Chain Sequences:. *Chain A:. Sequence, ... Uniprot Q14451 (Start-119) Domains in SCOPe 2.08: d4wwqa_*Chain B:. Compound: Growth factor receptor-bound protein 7. Species ...

http://scop.berkeley.edu/pdb/code=4wwq

src Homology Domains G6.184.603.790.709.610.800 G6.184.603.790.709.610.640.750. State Government I1.409.775. N3.540.348.875. ... Catalytic Domain G6.184.603.60.125 G6.184.603.790.709.610.189. Cataract Extraction E4.540.208 E4.540.825.249. Caudate Nucleus ...

https://decs.bvs.br/P/mnchg2008.htm

... of the Fyn SH3 domain demonstrated the requirement for an acidic cluster at the C-terminus of the RT-Src loop of the SH3 domain ... We conclude that the NS5A:Fyn SH3 domain interaction occurs via a canonical SH3 domain binding site and the high affinity of ... coli and examined their interactions with the SH3 domain of the Src-family tyrosine kinase, Fyn. Surface plasmon resonance ... analysis revealed that NS5A binds to the Fyn SH3 domain with what can be considered a high affinity SH3 domain-ligand ...

https://virologyj.biomedcentral.com/articles/10.1186/1743-422X-5-24

SHC (Src homology 2 domain containing) transforming protein 1. SHC1. 200. SIN3A. SIN3 transcription regulator family member A. ... Sad1 and UNC84 domain containing 1. SUN1. 180. TAF1. TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor, ... STIP1 homology and U-box containing protein 1, E3 ubiquitin protein ligase. STUB1. ...

https://genomics.senescence.info/genes/query.php?show=4&sort=2

Phosphorylated IRS-1 or IRS-2 can bind to the I4R motif and then serve as a docking protein for many src-homology 2 (SH2) ... The intracellular domain of the IL-4Rα contains an I4R motif that is also present in the insulin and IGF-1 receptors. ... This is followed by widely spaced clusters of exons encoding the constant-region domains of each of the heavy chain isotypes. ... Box 1 and box 2 motifs, conserved sequences present in the intracellular domains of receptors that signal via JAK kinases, are ...

https://www.jci.org/articles/view/8205/version/1

Avhandlingar om PLECKSTRIN HOMOLOGY PH DOMAIN. Sök bland 106693 avhandlingar från svenska högskolor och universitet på ... a cytoplasmic enzyme related to the Src family of kinases. LÄS MER ... Sökning: Pleckstrin Homology PH domain. Hittade 4 avhandlingar innehållade orden Pleckstrin Homology PH domain. . ... Microtubule Interacting and Trafficking MIT domain; Pleckstrin Homology PH domain; Biotechnology; Bioteknologi; ...

https://www.avhandlingar.se/om/Pleckstrin+Homology+PH+domain/

1995) A single point mutation switches the specificity of group III Src homology (SH) 2 domains to that of group I SH2 domains. ... A,Alignment of chimaerin SH2 domain with Src SH2 domain. Notation above the alignment refers to SH2 domain secondary structure ... a novel plekstrin homology and Src homology 3 domain containing RhoGAP protein. J Cell Biol 152:971-983. ... α-Chimaerin, a Rac/Cdc42 regulator, occurs as α1- and alternatively spliced Src homology 2 (SH2) domain-containing α2-isoforms ...

https://www.jneurosci.org/content/21/14/5191

IL-10 inhibits CD28 and ICOS costimulations of T cells via src homology 2 domain-containing protein tyrosine phosphatase 1. J ... Adiponectin shares sequence homology with a complement system protein (C1q) and structural homology with TNF family members ( ...

https://www.frontiersin.org/articles/10.3389/fimmu.2014.00457/full

Interactions with Rab3 and a new class of Src homology 3 domain proteins. J Biol Chem. 275:20033-20044. 2000.PubMed/NCBI ... contain the full complement of domains which are the N-terminal Zn2+-finger domain, the central PDZ and C2A domains and the C- ... Wang Y, Sugita S and Südhof TC: The RIM/NIM family of neuronal C2domain proteins. ... terminal C2B domain (15). They are able to bind to Rab3 and Munc13 proteins (13,21,22) and closely interact with α-liprins (13 ...

https://www.spandidos-publications.com/br/1/4/619

src Homology Domains 32% * Jurkat Cells 32% * Protein C 30% * Proline 19% ...

https://mayoclinic.pure.elsevier.com/en/publications/the-c-terminus-of-t-cell-specific-adapter-protein-tsad-is-necessa/fingerprints/

Curcumin suppresses Janus kinase-STAT inflammatory signaling through activation of Src homology 2 domain-containing tyrosine ...

https://www.mdpi.com/2076-3921/5/4/40

src Homology Domains Medicine & Life Sciences 56% * Protein Chemical Compounds 38% * WW Domains Medicine & Life Sciences 36% ... In this article, we analyse the binding of the p53 proline-rich region with a pool of selected polyproline binding domains (i.e ... In this article, we analyse the binding of the p53 proline-rich region with a pool of selected polyproline binding domains (i.e ... In this article, we analyse the binding of the p53 proline-rich region with a pool of selected polyproline binding domains (i.e ...

https://moh-it.pure.elsevier.com/en/publications/the-adapter-protein-cd2ap-binds-to-p53-protein-in-the-cytoplasm-a

An SH2-SH3 domain hybrid. Russell, R. B. & Barton, G. J., 26 Aug 1993, In: Nature. 364, 6440, p. 765 1 p.. Research output: ...

https://discovery.dundee.ac.uk/en/organisations/computational-biology/publications/?page=4&ordering=type&descending=false

... signal through co-stimulatory molecules CD28 and ICOS is hampered by src homology 2 domain-containing protein tyrosine ... transmembrane domain deleted) compared with chronic asthmatics or healthy individuals, which decreases with corticosteroid ...

https://www.medscape.com/viewarticle/812906_8

Src-homology 2 domain-containing phosphatase (SHP)-1 is important in regulating immune responses and cell survival. However, ...

https://pesquisa.bvsalud.org/portal/?lang=pt&q=mh:%22Monofosfato%20de%20Adenosina/metabolismo%22

Src homology region 2 domain-containing phosphatase-1. SIRT:. Sirtuin. TNF-α:. Tumor necrosis factor-α ... HNF-1α contains 3 functional domains, N-terminal dimerization domain (between residues 1 and 32), a bipartite DNA-binding motif ... Sequence homology and NMR have confirmed the coiled-coil or a four-helix bundle structure of HNF-1α and HNF-1β. ... There are four different structural classes of HNF primarily based on their DNA binding domain (DBD), namely HNF1, HNF3 (FOXA ...

https://stemcellres.biomedcentral.com/articles/10.1186/s13287-019-1438-z

... src homology 2) and SH3 domains. PH domains have been shown to bind the beta gamma-subunits of G-proteins and ... The pleckstrin homology (PH) domain is extended in the Btk kinase family by a region designated the TH (Tec homology) domain, ... Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. The domains can bind ... SOLUTION STRUCTURE OF A PLECKSTRIN HOMOLOGY DOMAIN. 1pms. PLECKSTRIN HOMOLOGY DOMAIN OF SON OF SEVENLESS 1 (SOS1) WITH GLYCINE- ...

https://smart.embl.de/smart/do_annotation.pl?DOMAIN=PH&START=381&END=480&E_VALUE=1.02e-14&TYPE=SMART&BLAST=VSKKGYLHFKEPLSSNWAKHFVVVRRPYVFIYNSDKDPVERGIINLSTAQVEYSEDQQAMVKTPNTFAVCTKHRGVLLQALNDKDMNDWLYAFNPLLAGT

They then fused a high-affinity Src homology 2 (SH2) domain, which acts as a binding module for pY, to AtzC. This enabled them ...

https://www.technologynetworks.com/proteomics/articles/sculpting-never-ending-art-using-natures-natural-tools-proteins-322134

Identification and characterization of two novel SH2 domain-containing proteins from a yeast two hybrid screen with the ABL tyrosine kinase. (nih.gov)
Yeast src homology region 3 domain-binding proteins involved in bud formation. (rupress.org)
We show that activated RTKs terminate downstream signaling via the direct phosphorylation of an evolutionarily conserved Tyr present in most SRC homology (SH) 3 domains, which are often part of key hub proteins for RTK-dependent signaling. (inrs.ca)
The hepatitis C virus (HCV) non-structural 5A protein (NS5A) contains a highly conserved C-terminal polyproline motif with the consensus sequence Pro-X-X-Pro-X-Arg that is able to interact with the Src-homology 3 (SH3) domains of a variety of cellular proteins. (biomedcentral.com)
We, and others, have shown that these motifs (termed PP2.1 and PP2.2) bind to the Src homology 3 (SH3) domains of a range of cellular proteins. (biomedcentral.com)
Though these proteins share similar DNA-binding characteristics, their activation domains are distinct. (biomedcentral.com)
For the same reason, homodimers of HNF-1α and HNF-1β trigger the transcription, while heterodimers of these two proteins have a potential to block HNF-1α-dependent genes as some isoforms of HNF-1β are deficient in activation domain. (biomedcentral.com)
Domain commonly found in eukaryotic signalling proteins. (embl.de)
The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)
There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
Taxonomic distribution of proteins containing PH domain. (embl.de)
The complete taxonomic breakdown of all proteins with PH domain is also avaliable . (embl.de)
Click on the protein counts, or double click on taxonomic names to display all proteins containing PH domain in the selected taxonomic class. (embl.de)
GRB10 is an imprinted, SH2 domain-containing, adaptor protein which binds with receptor tyrosine kinases, including the insulin receptor and insulin growth factor- (IGF-) 1R, and interferes with IRS-1/2 activation by interactions with SH2 domain-containing proteins [ 4 , 15 - 18 ]. (hindawi.com)
The name Janus kinase refers to the fact the proteins have two phosphate-transferring domains. (nih.gov)
Src homology 2 (SH2) domains play an essential role in cellular signal transduction by binding to proteins phos-phorylated on Tyr residue. (uwo.ca)
Polyproline repeats within the proline-rich region provide possible sites for the binding of numerous Src-homology 3 (SH3)-domain-containing proteins (see poster) ( Takenawa and Suetsugu, 2007 ). (biologists.com)
High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains. (google.ru)
OmpA-like transmembrane domain is an evolutionarily conserved domain of outer membrane proteins. (igem.org)
A BCL-2-like protein that has a C-terminal BCL-2 homology (BH3) domain and forms heterodimers with other BCL-2 FAMILY PROTEINS. (nih.gov)

Boi2p has a proline-rich sequence that is critical for displaying the Boi2p-Bem1p two-hybrid interaction, an SH3 domain in its NH2-terminal half, and a pleckstrin homology domain in its COOH-terminal half. (rupress.org)
Analysis using several truncated versions of BOI2 revealed that the COOH-terminal half, which contains the pleckstrin homology domain is essential for the function of Boi2p in cell growth, while the NH2-terminal half is not, and the NH2-terminal half might be required for modulating the function of Bem1p. (rupress.org)
Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)

The defective gene causing XLA is the BTK gene, which codes for the protein Bruton s tyrosine kinase (Btk), a cytoplasmic enzyme related to the Src family of kinases. (avhandlingar.se)
Grb7 is an adaptor-type signalling protein that is recruited via its Src-homology 2 (SH2) domain to a variety of tyrosine kinases. (garvan.org.au)
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. (bvsalud.org)
This cilia in the life of the serine by receptor fusion kinases of the Src neddylation( 1). (erik-mill.de)

Shp-1 is one of two human "Src Homology-2 (SH2) containing phosphatases", enzymes in which two regulatory phosphotyrosine binding domains (N-SH2 & C-SH2) lie N-terminal to the catalytic (PTP) domain. (enzolifesciences.com)

The structures of domains II and III remain undetermined but of particular interest is the observation that the flexible linker between these domains contains two motifs with the consensus sequence Pro-X-X-Pro-X-Arg/Lys. (biomedcentral.com)
Sequence homology and NMR have confirmed the coiled-coil or a four-helix bundle structure of HNF-1α and HNF-1β. (biomedcentral.com)
Inspection of the sequence of Sab reveals the presence of two putative mitogen-activated protein kinase interaction motifs (KIMs) similar to that found in the JNK docking domain of the c-Jun transcription factor, and four potential serine-proline JNK phosphorylation sites in the C-terminal half of the molecule. (portlandpress.com)
Although Tyr phosphorylation (pY) is a prerequisite for binding for essentially all SH2 domains characterized to date, different SH2 domains prefer specific sequence motifs C-terminal to the pY residue. (uwo.ca)
Because all SH2 domains adopt the same structural fold, it is not well understood how different SH2 domains have acquired the ability to recognize distinct sequence motifs. (uwo.ca)
Furthermore, we found that the specificity of a given variant correlates with the sequence feature of the bait peptide used for its isolation, suggesting that an SH2 domain may acquire specificity by co-evolving with its ligand. (uwo.ca)

Mutagenic analysis of the Fyn SH3 domain demonstrated the requirement for an acidic cluster at the C-terminus of the RT-Src loop of the SH3 domain, as well as several highly conserved residues previously shown to participate in SH3 domain peptide binding. (biomedcentral.com)
An injectable physical blend of hyaluronan and methylcellulose (HAMC) was covalently modified with a peptide binding partner of the Src homology 3 (SH3) domain. (bvsalud.org)
This domain was expressed as a fusion protein with RdCVFL, thereby enabling its controlled release from HAMC-binding peptide. (bvsalud.org)

Understanding the specificity of Src homology 2 (SH2) domains is important because of their critical role in cell signaling. (rcsb.org)
We have shown previously that the EF and BG loops that connect the secondary structure elements on an SH2 domain dictate its specificity. (uwo.ca)
By characterizing a group of SH2 variants selected by different pY peptides from phage-displayed libraries, we show that the EF and BG loops of the Fyn SH2 domain can encode a wide spectrum of specificities, including all three major specificity classes (p 2, p 3 and p 4) of the SH2 domain family. (uwo.ca)
Our work provides a plausible mechanism for the SH2 domain to acquire the wide spectrum of specificity observed in nature through loop variation with minimal disturbance to the SH2 fold. (uwo.ca)
It is likely that similar mechanisms may have been employed by other modular interaction domains to generate diversity in specificity. (uwo.ca)

Src homology 2 domain-containing protein tyrosine phosphatase 2 (SHP2) is an evolutionarily conserved protein tyrosine phosphatase with a widespread expression pattern16. (groundwater-2011.net)

Surface plasmon resonance analysis revealed that NS5A binds to the Fyn SH3 domain with what can be considered a high affinity SH3 domain-ligand interaction (629 nM), and this binding did not require the presence of domain I of NS5A (amino acid residues 32-250). (biomedcentral.com)

Sab binds to and serves as a substrate for JNK in vitro , and was previously found to interact with the Src homology 3 (SH3) domain of Bruton's tyrosine kinase (Btk). (portlandpress.com)
We fused HIV-protease with OmpA and expressed it in a second E. coli strain which we immobilize at the destination, so substrate (together with SH3 domain) could be released once the E. colimousine arrives there. (igem.org)

DCoH (transcriptional coactivator dimerization cofactor) blocks subunit exchange by associating with the dimerization domain. (biomedcentral.com)

In humans, a common polymorphism determines the identity of residue 72, either proline or arginine, and affects the features of the motifs present in the polyproline domain. (elsevier.com)
In this article, we analyse the binding of the p53 proline-rich region with a pool of selected polyproline binding domains (i.e. (elsevier.com)

[ 4 ] The genetic defect appears to be a region of the gene encoding the KRT14 nonhelical head (E1/V1) domain located between the microsatellite markers D17S798 and D17S957, which are separated by approximately 26.97 cM. (medscape.com)
This target gene encodes the protein 'intersectin 1' in humans and may also be known as ITSN, Sh3, SH3D1A, SH3P17, SH3 domain-containing protein 1A, and Src homology 3 domain-containing protein. (biocompare.com)
In support of this idea are the linea that the colorectal tumor suppressor protein DCC has some structural homology to LAR438 and that the LAR gene maps to a linds on chromosome 1p32-33 that is thought e contain a breast cancer tumor sup- pressor gene. (qrforex.com)

This family of SOCS contains eight members, SOCS1-7 and cytokine-inducible SH2-containing protein (CIS/CISH), which are characterized by the presence of similar structural domains that include a central SH2 (Src Homology 2) domain, a C-terminal SOCS box region, and an N-terminal region of variable length. (researchsquare.com)

The SH1 domain is a CATALYTIC DOMAIN . (bvsalud.org)

SH2 and SH3 domains are protein interaction domains. (bvsalud.org)

Nephrin-like domains of IL2RG in enzymes lack NAD-dependent umbilical neuronal absence( X-SCID), which activates a distress of also regulated goal and NOTCH2 fuel( synaptic) receptor eNOS, but synthetic tethers of B substrates. (erik-mill.de)

[ 111 ] Patients with acute asthma have higher levels of soluble CD86 (transmembrane domain deleted) compared with chronic asthmatics or healthy individuals, which decreases with corticosteroid treatment. (medscape.com)
2 As it lacks a transmembrane domain, it is anchored to the surface through glycophosphatidylinositol. (hcdm.org)

[ 113 ] In the presence of IL-10, signal through co-stimulatory molecules CD28 and ICOS is hampered by src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1) phosphorylation leading to tolerance. (medscape.com)

α-Chimaerin, a Rac/Cdc42 regulator, occurs as α1- and alternatively spliced Src homology 2 (SH2) domain-containing α2-isoforms. (jneurosci.org)
To determine whether α2-chimaerin may have a role in neuronal differentiation and the relevance of the SH2 domain, the morphological effects of both chimaerin isoforms were investigated in N1E-115 neuroblastoma cells. (jneurosci.org)

The yeast protein Bem1p, which bears two src homology region 3 (SH3) domains, is involved in cell polarization. (rupress.org)
A nonsense mutation in a corresponding region of KRT5 has been found in Dowling-Degos disease and a missense mutation in the V1 domain of KRT5 has been described in patients with epidermolysis bullosa with mottled pigmentation. (medscape.com)
It comprises one or two WASP homology 2 (WH2) domains, which bind to monomeric actin, followed by a short central (C) region and an acidic (A) domain, which interacts with the Arp2/3 complex. (biologists.com)

HNF-1α contains 3 functional domains, N-terminal dimerization domain (between residues 1 and 32), a bipartite DNA-binding motif having atypical POU-homeodomain (between residues 98 and 280), and a C-terminal transactivation domain (between residues 281 and 631) [ 2 ]. (biomedcentral.com)
There are no totally invariant residues within the PH domain. (embl.de)
Isoform gamma contains two PH domains, the second one is split into two parts separated by about 400 residues. (embl.de)

Upon stimulation with TLR2 ligands, MyD88 cis-Urocanic acid recruits IL-1 receptor-associated kinase-4 (IRAK-4) to TLR2 through conversation of the death domains of both molecules. (groundwater-2011.net)

SH3 and WW), and we present the first demonstration that the purified SH3 domains of the CD2AP/Cin85 protein family are able to directly bind the p53 protein, and to discriminate between the two polymorphic variants P72R. (elsevier.com)

Enhanced prediction of Src homology 2 (SH2) domain binding potentials using a fluorescence polarization-derived c-Met, c-Kit, ErbB, and androgen receptor interactome. (nih.gov)
death receptor variant: A-x-pY-x-x-L). This binding activates Shp-1 phosphatase by displacing an inhibitory interaction between the N-SH2 and PTP domains. (enzolifesciences.com)

Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.de)

The C-terminal SH3 domain of p67-phox has been shown to interact with the proline-rich domain of p47-phox, suggesting that p47-phox may faciliate the transport of p67-phox to the membrane. (diagenox.com)

To understand this interaction in more detail we have expressed two N-terminally truncated forms of NS5A in E. coli and examined their interactions with the SH3 domain of the Src-family tyrosine kinase, Fyn. (biomedcentral.com)
We conclude that the NS5A:Fyn SH3 domain interaction occurs via a canonical SH3 domain binding site and the high affinity of the interaction suggests that NS5A would be able to compete with cognate Fyn ligands within the infected cell. (biomedcentral.com)

IL2RG has of a glutamic transfer matrix and a processes( mental domain that controls a plasma size III( FNIII) subfamily termed to silence wasted in nutrient CDH1-mediated epiblast. (erik-mill.de)

Mutational analysis revealed that the second SH3 domain from the NH2 terminus (SH3-2) of Bem1p is important for the functions of Bem1p in bud formation and in the suppression of the rho3 defect. (rupress.org)

loop_ _audit_author.name _audit_author.pdbx_ordinal 'Enmon, J.L.' 1 'De Beer, T.' 2 'Overduin, M.' 3 # _citation.id primary _citation.title ;Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites. (rcsb.org)

Surface loops in a single SH2 domain are capable of encoding the spect" by Huadong Liu, Haiming Huang et al. (uwo.ca)

Src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2) of gastric epithelial cells interacts with cagA from Helicobacter pylori (H. pylori). (who.int)

We expressed RdCVFL as a fusion protein with an Src homology 3 domain (SH3). (bvsalud.org)

The three-dimensional structure of domain I has been determined and it has been shown to complex with a zinc ion and (at least in the crystal structure) exists as a dimer [ 5 ]. (biomedcentral.com)
the E-value for the PH domain shown below is 1.02e-14. (embl.de)

CD150 associates with the src homology 2-domain-containing protein tyrosine phosphatase SHP-2, and this association is thought to be involved in signal transduction. (biolegend.com)

Anatomy18

Organisms7

Chemicals and Drugs103

Analytical, Diagnostic and Therapeutic Techniques and Equipment23

Phenomena and Processes48

Information Science4

Cryo-electron microscopy structure of an SH3 amyloid fibril and model of the molecular packing. (1/3051)

Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation. (2/3051)

Anopheles gambiae Ag-STAT, a new insect member of the STAT family, is activated in response to bacterial infection. (3/3051)

DEF-1, a novel Src SH3 binding protein that promotes adipogenesis in fibroblastic cell lines. (4/3051)

Identification of a new Pyk2 target protein with Arf-GAP activity. (5/3051)

Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Involvement of Jak2 in the stimulation of phosphatidylinositol 3-kinase. (6/3051)

C-terminal Src kinase associates with ligand-stimulated insulin-like growth factor-I receptor. (7/3051)

Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck. (8/3051)

src Homology Domains

Protein Tyrosine Phosphatase, Non-Receptor Type 6

Protein Tyrosine Phosphatase, Non-Receptor Type 11

Tyrosine

Protein Tyrosine Phosphatases

Adaptor Proteins, Signal Transducing

Amino Acid Sequence

Molecular Sequence Data

Protein Binding

Phosphorylation

Protein-Tyrosine Kinases

Intracellular Signaling Peptides and Proteins

Signal Transduction

Sequence Homology, Amino Acid

Phosphoproteins

Protein Structure, Tertiary

Binding Sites

Recombinant Fusion Proteins

src-Family Kinases

Cloning, Molecular

Base Sequence

Blood Proteins

Sequence Alignment

Cell Line

Carrier Proteins

Amino Acid Motifs

Recombinant Proteins

Transfection

Sequence Homology, Nucleic Acid

Phosphotyrosine

Proto-Oncogene Proteins pp60(c-src)

Phosphatidylinositol Phosphates

GRB2 Adaptor Protein

Mutagenesis, Site-Directed

COS Cells

Models, Molecular

Phospholipase C delta

DNA, Complementary

SH2 Domain-Containing Protein Tyrosine Phosphatases

Protein Conformation

Proto-Oncogene Proteins

Enzyme Activation

Guanine Nucleotide Exchange Factors

Membrane Proteins

Protein Interaction Domains and Motifs

Mutation

Two-Hybrid System Techniques

Glutathione Transferase

Protein Structure, Secondary

Phospholipase C gamma

Proteins

Cell Membrane

3T3 Cells

Structure-Activity Relationship

DNA-Binding Proteins

Adaptor Proteins, Vesicular Transport

Conserved Sequence

Proline

Precipitin Tests

Phosphatidylinositol 4,5-Diphosphate

Dynamins

Sequence Homology

Structural Homology, Protein

Microfilament Proteins

Type C Phospholipases

Oncogene Protein pp60(v-src)

Phosphatidylinositol 3-Kinases

Sequence Deletion

Crystallography, X-Ray

Proto-Oncogene Proteins c-fyn

Protein Transport

Peptide Fragments

GTPase-Activating Proteins

Dimerization

DNA Primers

Phosphoric Monoester Hydrolases

Transcription Factors

Ligands

Proto-Oncogene Proteins c-crk

Genes, src