A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
A 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
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 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 SH2 DOMAIN-containing protein that mediates SIGNAL TRANSDUCTION pathways from multiple CELL SURFACE RECEPTORS, including the EPHB1 RECEPTOR. It interacts with FOCAL ADHESION KINASE and is involved in CELL MIGRATION.
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.
An adaptor protein complex primarily involved in the formation of clathrin-related endocytotic vesicles (ENDOSOMES) at the CELL MEMBRANE.
An adaptor protein complex found primarily on perinuclear compartments.
A clathrin adaptor protein complex primarily involved in clathrin-related transport at the TRANS-GOLGI NETWORK.
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 family of large adaptin protein subunits of approximately 100 kDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 2.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A family of large adaptin protein complex subunits of approximately 90-130 kDa in size.
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.
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.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A family of medium adaptin protein subunits of approximately 45 KDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 3 and ADAPTOR PROTEIN COMPLEX 4.
An adaptor protein complex involved in transport of molecules between the TRANS-GOLGI NETWORK and the endosomal-lysosomal system.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
A family of large adaptin protein subunits of approximately 90 KDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 1.
A class of RAS GUANINE NUCLEOTIDE EXCHANGE FACTORS that are genetically related to the Son of Sevenless gene from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The main structural coat protein of COATED VESICLES which play a key role in the intracellular transport between membranous organelles. Each molecule of clathrin consists of three light chains (CLATHRIN LIGHT CHAINS) and three heavy chains (CLATHRIN HEAVY CHAINS) that form a structure called a triskelion. Clathrin also interacts with cytoskeletal proteins.
Transport proteins that carry specific substances in the blood or across cell membranes.
The subunits that make up the large, medium and small chains of adaptor proteins.
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 level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A family of large adaptin protein subunits of approximately 130-kDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 3.
An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES.
A death domain receptor signaling adaptor protein that plays a role in signaling the activation of INITIATOR CASPASES such as CASPASE 2. It contains a death domain that is specific for RIP SERINE-THEONINE KINASES and a caspase-binding domain that binds to and activates CASPASES such as CASPASE 2.
Established cell cultures that have the potential to propagate indefinitely.
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.
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.
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.
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.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
The 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.
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.
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.
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
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).)
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
Vesicles formed when cell-membrane coated pits (COATED PITS, CELL-MEMBRANE) invaginate and pinch off. The outer surface of these vesicles is covered with a lattice-like network of the protein CLATHRIN. Shortly after formation, however, the clathrin coat is removed and the vesicles are referred to as ENDOSOMES.
A family of small adaptin protein complex subunits of approximately 19 KDa in size.
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.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
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.
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.
Cell surface receptors that are specific for INTERLEUKIN-1. Included under this heading are signaling receptors, non-signaling receptors and accessory proteins required for receptor signaling. Signaling from interleukin-1 receptors occurs via interaction with SIGNAL TRANSDUCING ADAPTOR PROTEINS such as MYELOID DIFFERENTIATION FACTOR 88.
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 phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.
A subclass of clathrin assembly proteins that occur as monomers.
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.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A family of intracellular signaling adaptor proteins that contain caspase activation and recruitment domains. Proteins that contain this domain play a role in APOPTOSIS-related signal transduction by associating with other CARD domain-containing members and in activating INITIATOR CASPASES that contain CARD domains within their N-terminal pro-domain region.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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.
Cytoplasmic vesicles formed when COATED VESICLES shed their CLATHRIN coat. Endosomes internalize macromolecules bound by receptors on the cell surface.
A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A network of membrane compartments, located at the cytoplasmic side of the GOLGI APPARATUS, where proteins and lipids are sorted for transport to various locations in the cell or cell membrane.
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.
Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.
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.
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.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
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.
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.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
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.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.
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 signal-transducing adaptor protein that associates with TNF RECEPTOR complexes. It contains a death effector domain that can interact with death effector domains found on INITIATOR CASPASES such as CASPASE 8 and CASPASE 10. Activation of CASPASES via interaction with this protein plays a role in the signaling cascade that leads to APOPTOSIS.
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 transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
A 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.
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.
A protein tyrosine kinase that is required for T-CELL development and T-CELL ANTIGEN RECEPTOR function.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Glycoproteins found on the membrane or surface of cells.
A family of GUANINE NUCLEOTIDE EXCHANGE FACTORS that are specific for RAS PROTEINS.
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.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
Proteins prepared by recombinant DNA technology.
Specialized regions of the cell membrane composed of pits coated with a bristle covering made of the protein CLATHRIN. These pits are the entry route for macromolecules bound by cell surface receptors. The pits are then internalized into the cytoplasm to form the COATED VESICLES.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A mammalian homolog of the DROSOPHILA SON OF SEVENLESS PROTEIN. It is a guanine nucleotide exchange factor for RAS PROTEINS.
A negative regulator of the CELL CYCLE that undergoes PHOSPHORYLATION by CYCLIN-DEPENDENT KINASES. RBL2 contains a conserved pocket region that binds E2F4 TRANSCRIPTION FACTOR and E2F5 TRANSCRIPTION FACTOR. RBL2 also interacts with viral ONCOPROTEINS such as POLYOMAVIRUS TUMOR ANTIGENS; ADENOVIRUS E1A PROTEINS; and PAPILLOMAVIRUS E7 PROTEINS.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
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)
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.
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.
Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.
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 large class of structurally-related proteins that contain one or more LIM zinc finger domains. Many of the proteins in this class are involved in intracellular signaling processes and mediate their effects via LIM domain protein-protein interactions. The name LIM is derived from the first three proteins in which the motif was found: LIN-11, Isl1 and Mec-3.
A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.
Macromolecular complexes formed from the association of defined protein subunits.
Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.
The act of ligating UBIQUITINS to PROTEINS to form ubiquitin-protein ligase complexes to label proteins for transport to the PROTEASOME ENDOPEPTIDASE COMPLEX where proteolysis occurs.
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 large family of signal-transducing adaptor proteins present in wide variety of eukaryotes. They are PHOSPHOSERINE and PHOSPHOTHREONINE binding proteins involved in important cellular processes including SIGNAL TRANSDUCTION; CELL CYCLE control; APOPTOSIS; and cellular stress responses. 14-3-3 proteins function by interacting with other signal-transducing proteins and effecting changes in their enzymatic activity and subcellular localization. The name 14-3-3 derives from numerical designations used in the original fractionation patterns of the proteins.
Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.
Intracellular signaling adaptor proteins that play a role in the coupling of SYNDECANS to CYTOSKELETAL PROTEINS.
Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
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.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A guanine nucleotide exchange factor from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.
A signal transducing tumor necrosis factor receptor associated factor that is involved in regulation of NF-KAPPA B signalling and activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES.
A family of structurally related proteins that were originally discovered for their role in cell-cycle regulation in CAENORHABDITIS ELEGANS. They play important roles in regulation of the CELL CYCLE and as components of UBIQUITIN-PROTEIN LIGASES.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
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.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A 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)
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.
The heavy chain subunits of clathrin.
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.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
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.
Vesicles formed when cell-membrane coated pits (COATED PITS, CELL-MEMBRANE) invaginate and pinch off. The outer surface of these vesicles are covered with a lattice-like network of coat proteins, such as CLATHRIN, coat protein complex proteins, or CAVEOLINS.
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
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.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
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 pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
Regulatory proteins that down-regulate phosphorylated G-protein membrane receptors, including rod and cone photoreceptors and adrenergic receptors.
Adherence of cells to surfaces or to other cells.
An ATP-dependent protease found in prokaryotes, CHLOROPLASTS, and MITOCHONDRIA. It is a soluble multisubunit complex that plays a role in the degradation of many abnormal proteins.
An oncoprotein from the Cas NS-1 murine retrovirus that induces pre- B-CELL LYMPHOMA and MYELOID LEUKEMIAS. v-cbl protein is a tyrosine-phosphorylated, truncated form of its cellular homologue, PROTO-ONCOGENE PROTEIN C-CBL.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Intracellular signaling adaptor proteins that bind to the cytoplasmic death domain region found on DEATH DOMAIN RECEPTORS. Many of the proteins in this class take part in intracellular signaling from TUMOR NECROSIS FACTOR RECEPTORS.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
A cell line derived from cultured tumor cells.
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.
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 movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
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.
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.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Vesicles that are involved in shuttling cargo from the interior of the cell to the cell surface, from the cell surface to the interior, across the cell or around the cell to various locations.
A 34 kDa signal transducing adaptor protein that associates with TUMOR NECROSIS FACTOR RECEPTOR TYPE 1. It facilitates the recruitment of signaling proteins such as TNF RECEPTOR-ASSOCIATED FACTOR 2 and FAS ASSOCIATED DEATH DOMAIN PROTEIN to the receptor complex.
A signal transducing tumor necrosis factor receptor associated factor that is involved in TNF RECEPTOR feedback regulation. It is similar in structure and appears to work in conjunction with TNF RECEPTOR-ASSOCIATED FACTOR 1 to inhibit APOPTOSIS.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
Cleavage of proteins into smaller peptides or amino acids either by PROTEASES or non-enzymatically (e.g., Hydrolysis). It does not include Protein Processing, Post-Translational.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
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.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Surface ligands that mediate cell-to-cell adhesion and function in the assembly and interconnection of the vertebrate nervous system. These molecules promote cell adhesion via a homophilic mechanism. These are not to be confused with NEURAL CELL ADHESION MOLECULES, now known to be expressed in a variety of tissues and cell types in addition to nervous tissue.
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.
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
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.
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.
Detergent-insoluble CELL MEMBRANE components. They are enriched in SPHINGOLIPIDS and CHOLESTEROL and clustered with glycosyl-phosphatidylinositol (GPI)-anchored proteins.
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.
Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.
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.
A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.
An anchoring junction of the cell to a non-cellular substrate. It is composed of a specialized area of the plasma membrane where bundles of the ACTIN CYTOSKELETON terminate and attach to the transmembrane linkers, INTEGRINS, which in turn attach through their extracellular domains to EXTRACELLULAR MATRIX PROTEINS.
A pattern recognition receptor that binds DOUBLE-STRANDED RNA. It mediates cellular responses to certain viral pathogens.
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.
An interferon regulatory factor that is expressed constitutively and undergoes POST-TRANSLATIONAL MODIFICATION following viral infection. PHOSPHORYLATION of IRF-3 causes the protein to be translocated from the CYTOPLASM to CELL NUCLEUS where it binds DNA, and activates transcription.
A class of morphologically heterogeneous cytoplasmic particles in animal and plant tissues characterized by their content of hydrolytic enzymes and the structure-linked latency of these enzymes. The intracellular functions of lysosomes depend on their lytic potential. The single unit membrane of the lysosome acts as a barrier between the enzymes enclosed in the lysosome and the external substrate. The activity of the enzymes contained in lysosomes is limited or nil unless the vesicle in which they are enclosed is ruptured. Such rupture is supposed to be under metabolic (hormonal) control. (From Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
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.
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.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
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.
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.
Methods for determining interaction between PROTEINS.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A signal transducing tumor necrosis factor receptor associated factor that is involved in TNF RECEPTOR feedback regulation. It is similar in structure and appears to work in conjunction with TNF RECEPTOR-ASSOCIATED FACTOR 2 to inhibit APOPTOSIS.
A genetically related subfamily of RAP GTP-BINDING PROTEINS that share homology with RAS PROTEINS. They bind to Ras effectors but do not activate them, therefore they may antagonize the effects of RAS PROTEINS. This enzyme was formerly listed as EC 3.6.1.47.
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.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of a N-terminal catalytic domain and a large C-terminal domain that is enriched in PROLINE, GLUTAMIC ACID, SERINE, and THREONINE residues (PEST sequences). The phosphatase subtype is ubiquitously expressed and implicated in the regulation of a variety of biological processes such as CELL MOVEMENT; CYTOKINESIS; focal adhesion disassembly; and LYMPHOCYTE ACTIVATION.

Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis. (1/915)

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

Polarized distribution of Bcr-Abl in migrating myeloid cells and co-localization of Bcr-Abl and its target proteins. (2/915)

Bcr-Abl plays a critical role in the pathogenesis of Philadelphia chromosome-positive leukemia. Although a large number of substrates and interacting proteins of Bcr-Abl have been identified, it remains unclear whether Bcr-Abl assembles multi-protein complexes and if it does where these complexes are within cells. We have investigated the localization of Bcr-Abl in 32D myeloid cells attached to the extracellular matrix. We have found that Bcr-Abl displays a polarized distribution, colocalizing with a subset of filamentous actin at trailing portions of migrating 32D cells, and localizes on the cortical F-actin and on vesicle-like structures in resting 32D cells. Deletion of the actin binding domain of Bcr-Abl (Bcr-AbI-AD) dramatically enhances the localization of Bcr-Abl on the vesicle-like structures. These distinct localization patterns of Bcr-Abl and Bcr-Abl-AD enabled us to examine the localization of Bcr-Abl substrate and interacting proteins in relation to Bcr-Abl. We found that a subset of biochemically defined target proteins of Bcr-Abl redistributed and co-localized with Bcr-Abl on F-actin and on vesicle-like structures. The co-localization of signaling proteins with Bcr-Abl at its sites of localization supports the idea that Bcr-Abl forms a multi-protein signaling complex, while the polarized distribution and vesicle-like localization of Bcr-Abl may play a role in leukemogenesis.  (+info)

Growth inhibition of breast cancer cells by Grb2 downregulation is correlated with inactivation of mitogen-activated protein kinase in EGFR, but not in ErbB2, cells. (3/915)

Increased breast cancer growth has been associated with increased expression of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases (RTKs). Upon activation, RTKs may transmit their oncogenic signals by binding to the growth factor receptor bound protein-2 (Grb2), which in turn binds to SOS and activates the Ras/Raf/MEK/mitogen-activated protein (MAP) kinase pathway. Grb2 is important for the transformation of fibroblasts by EGFR and ErbB2; however, whether Grb2 is also important for the proliferation of breast cancer cells expressing these RTKs is unclear. We have used liposomes to deliver nuclease-resistant antisense oligodeoxynucleotides (oligos) specific for the GRB2 mRNA to breast cancer cells. Grb2 protein downregulation could inhibit breast cancer cell growth; the degree of growth inhibition was dependent upon the activation and/or endogenous levels of the RTKs. Grb2 inhibition led to MAP kinase inactivation in EGFR, but not in ErbB2, breast cancer cells, suggesting that different pathways might be used by EGFR and ErbB2 to regulate breast cancer growth.  (+info)

Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation. (4/915)

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)

The tyrosines in the bidentate motif of the env-sea oncoprotein are essential for cell transformation and are binding sites for Grb2 and the tyrosine phosphatase SHP-2. (5/915)

The transforming gene product of the S13 avian erythroblastosis virus, the env-sea protein, is a member of the hepatocyte growth factor receptor family of tyrosine kinases comprising Met, Ron, and Sea. Like all three members of this family, the env-sea protein has a so-called bidentate motif (Y557INMAVTY564VNL) composed of two tandemly arranged tyrosines in the carboxyl terminus. To investigate whether the tyrosine residues in this motif are essential for the env-sea-mediated transformation, we generated tyrosine to phenylalanine mutations. Substitutions of both tyrosine residues resulted in complete loss of the transforming activity. In contrast, single mutations at either tyrosine did not inhibit transformation of Rat1 cells, and mutation of tyrosine 564 actually increased transformation of Rat 1 cells. To define signaling pathways activated by the env-sea protein, we looked for protein-protein interactions mediated by these tyrosine residues. We show that the bidentate motif is responsible for interaction with the adapter protein Grb2, phosphatidylinositol 3-kinase, and the tyrosine phosphatase SHP-2. Furthermore, we show that microinjected Src homology 2 domains from either Grb2 or SHP-2 blocked the transforming activity of the env-sea protein. Together, these results suggest that the tyrosines within the bidentate motif are essential for the env-sea transformation.  (+info)

Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and their association with Grb2 and Shc in Baf3/Flt3 cells. (6/915)

Flt3 ligand (FL) is an early-acting potent co-stimulatory cytokine that regulates proliferation and differentiation of a number of blood cell lineages. Its receptor Flt3/Flk2 belongs to class III receptor tyrosine kinases that also include the receptors for colony-stimulating factor 1, Steel factor, and platelet-derived growth factor. Using CSF-1 receptor/Flt3 chimeras, two groups have characterized some of the post-receptor signaling events and substrate specificity of murine Flt3 receptor. However, there are few studies on the signaling pathway through human Flt3. We examined human Flt3 signaling pathways in a murine IL-3-dependent hematopoietic cell line Baf3, which stably expresses full-length human Flt3 receptor. This subline proliferates in response to human FL. Like the chimeric murine Flt3, human Flt3 undergoes autophosphorylation, associates with Grb2, and leads to tyrosine phosphorylation of Shc on ligand binding. We found that SHP-2, but not SHP-1, is tyrosine-phosphorylated by FL stimulation. SHP-2 does not associate with Flt3, but binds directly to Grb2. SHIP is also tyrosine-phosphorylated and associates with Shc after FL simulation. We further examined the downstream signaling pathway. FL transiently activates MAP kinase. This activation could be blocked by PD98059, a specific MEK inhibitor. PD98059 also blocked cell proliferation in response to FL. These results demonstrate that SHP-2 and SHIP are important components in the human Flt3 signaling pathway and suggest that SHP-2 and SHIP, by forming complexes with adapter proteins Grb2 and Shc, may modulate MAP kinase activation, which may be necessary for the mitogenic signaling of Flt3.  (+info)

A differential requirement for the COOH-terminal region of the epidermal growth factor (EGF) receptor in amphiregulin and EGF mitogenic signaling. (7/915)

The epidermal growth factor receptor (EGFR) mediates the actions of a family of bioactive peptides that include epidermal growth factor (EGF) and amphiregulin (AR). Here we have studied AR and EGF mitogenic signaling in EGFR-devoid NR6 fibroblasts that ectopically express either wild type EGFR (WT) or a truncated EGFR that lacks the three major sites of autophosphorylation (c'1000). COOH-terminal truncation of the EGFR significantly impairs the ability of AR to (i) stimulate DNA synthesis, (ii) elicit Elk-1 transactivation, and (iii) generate sustained enzymatic activation of mitogen-activated protein kinase. EGFR truncation had no significant effect on AR binding to receptor but did result in defective GRB2 adaptor function. In contrast, EGFR truncation did not impair EGF mitogenic signaling, and in c'1000 cells EGF was able to stimulate the association of ErbB2 with GRB2 and SHC. Elk-1 transactivation was monitored when either ErbB2 or a truncated dominant-negative ErbB2 mutant (ErbB2-(1-813)) was overexpressed in cells. Overexpression of full-length ErbB2 resulted in a strong constitutive transactivation of Elk-1 in c'1000 but only slightly stimulated Elk-1 in WT or parental NR6 cells. Conversely, overexpression of ErbB2-(1-813) inhibited EGF-stimulated Elk-1 transactivation in c'1000 but not in WT cells. Thus, the cytoplasmic tail of the EGFR plays a critical role in AR mitogenic signaling but is dispensable for EGF, since EGF-activated truncated EGFRs can signal through ErbB2.  (+info)

Gi-mediated tyrosine phosphorylation of Grb2 (growth-factor-receptor-bound protein 2)-bound dynamin-II by lysophosphatidic acid. (8/915)

Lysophosphatidic acid (LPA) is the prototypic G-protein-coupled receptor agonist that activates the Ras-mitogen-activated protein (MAP) kinase cascade through pertussis toxin (PTX)-sensitive Gi and enhanced tyrosine kinase activity. We recently detected a 100 kDa protein (p100) that binds to the C-terminal SH3 domain of growth-factor-receptor-bound protein 2 (Grb2) and becomes tyrosine phosphorylated in a PTX-sensitive manner in LPA-treated Rat-1 cells [Kranenburg, Verlaan, Hordijk and Moolenaar (1997) EMBO J. 16, 3097-3105]. Through glutathione S-transferase-Grb2 affinity purification and microsequencing, we have now identified p100 as dynamin-II, a GTPase that regulates clathrin-mediated endocytosis. We show that in Rat-1 cells, Grb2-bound dynamin-II is rapidly tyrosine phosphorylated in response to LPA in a PTX-sensitive manner. Thus, tyrosine phosphorylation of Grb2-bound dynamin-II may be a critical event in Gi-mediated activation of the Ras-MAP kinase cascade in fibroblasts.  (+info)

TY - JOUR. T1 - Immunity to growth factor receptor-bound protein 10, a signal transduction molecule, inhibits the growth of breast cancer in mice. AU - O-Sullivan, In Sug. AU - Chopra, Amla. AU - Carr, Janai. AU - Tae, Sung Kim. AU - Cohen, Edward P.. PY - 2008/4/1. Y1 - 2008/4/1. N2 - This study describes the application of a unique strategy to identify breast cancer antigens [tumor-associated antigen (TAA)]. In a mouse model, the strategy led to the identification of growth factor receptor-bound protein 10 (Grb10) as a newly identified TAA. Grb10 is a signal transduction molecule associated with multiple transmembrane tyrosine kinase receptors. It was discovered by comparing microarrays of cellular breast cancer vaccines highly enriched for cells that induced breast cancer immunity in tumor-bearing mice with nonenriched vaccines. The vaccines were prepared by transferring a cDNA expression library derived from SB5b cells, a breast cancer cell line C3H/He origin (H-2k), into LM mouse ...
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GRB2 (Growth factor receptor-bound protein 2), Authors: Gagani Athauda, Donald P Bottaro. Published in: Atlas Genet Cytogenet Oncol Haematol.
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Aberrant activation of receptor tyrosine kinases, such as epidermal growth factor receptor (EGFR), plays a role in cancer initiation, progression, and acquired drug resistance. Genetic analysis may not always reveal aberrant activity of receptor tyrosine kinase signaling; thus, detecting active signaling through these kinases in clinical samples should improve prognostication and personalization of therapies. Diverse cancers, for example, those found in the lung, colon, or head and neck, can have aberrant activation of EGFR signaling, and EGFR-targeted therapies are used to treat these diseases. Smith et al. developed a proximity ligation assay (PLA) to detect the interaction between EGFR and the requisite signaling adaptor GRB2 (growth factor receptor-bound protein 2) in common clinical preparations. EGFR:GRB2 PLA recapitulated traditional readouts of active EGFR signaling in cultured cells, in a panel of tumor xenografts in mice derived from primary patient samples, and in samples from three ...
Complete information for GRB2 gene (Protein Coding), Growth Factor Receptor Bound Protein 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for GRB2 gene (Protein Coding), Growth Factor Receptor Bound Protein 2, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Binding of growth factor ligands to extracellular domain, RTKs induces receptor dimerization (forming either homodimers or heterodimers with other RTKs) followed by their autophosphorylation. This allows for subsequent recruitment of adaptor proteins such as growth factor receptor-bound protein 2 (GRB2), SRC homology 2 domain-containing protein (SHC), and Son of Sevenless (SOS) that activate proliferation, survival, and migration pathways (e.g., RAS, PI3K, SRC ...
1IO6: Solution Structure of the C-Terminal SH3 Domain of Grb2 Complexed with a Ligand Peptide: A Ligand Exchange Model of the SH3 Domain
Chronic myeloid leukemia is characterized by the Philadelphia (Ph1) translocation t(9;22) that generates a hybrid gene, bcr/abl, translated to a Mr210,000 tyrosine kinase (p210bcr/abl) with transforming activity for hematopoietic cells. Hematopoietic cell transformation by p210bcr/abl seems to involve activation of the Ras signaling pathway by at least two different signaling intermediates, growth factor receptor-bound protein 2 and Src homology and collagen protein, but additional signaling proteins are likely to be required as well. In an effort to identify additional phosphoproteins activated by p210bcr/abl, we studied the murine, interleukin 3-dependent, myeloid cell line, 32D, and a bcr/abl-transfected, factor-independent subline, 32Dp210. The analysis of whole-cell lysates of 32D and 32Dp210 cells showed that several proteins with a molecular weight of Mr50,000-60,000 were phosphorylated on tyrosine residues in 32Dp210 cells. Because Src family kinases have an apparent molecular weight of ...
Acute myeloid leukemia (AML) is characterized by the rapid accumulation of immature myeloid cells in the blood, resulting in a drop of the other cell types, such as red blood cells and platelets. Incidence increases with age, with a majority of patients aged 65 or older. AML is the most common acute leukemia in adults. The National Cancer Institute estimates that approximately 20,000 new cases occur each year. Approximately 36% of all leukemias are AML. There is a critically unmet need for non-toxic therapies for older, fragile AML patients who are unfit or ineligible for high-dose chemotherapy or a stem cell transplant. Remission rates for elderly AML patients is between 5-10% and only 5% of patients over the age of 65 will survive more than 5 years after diagnosis.. Prexigebersen (Liposomal Grb2 antisense) is Bio-Paths lead product candidate, a neutral-charge, liposome-incorporated antisense drug designed to inhibit protein synthesis of Grb2 (growth factor receptor bound protein 2). Grb2 ...
The goal of this clinical research study is to find the highest safe dose of BP1001 , a liposomal Growth Factor Receptor Bound Protein-2 antisense oligodeoxynucleotide (L-Grb2 AS), that can be given as treatment for patients with Ph+ CML, AML, ALL, or MDS. BP1001 is an antisense drug, which means it may help stop cancer cells by blocking the action of a protein that signals cancer cells to divide and increase in number. The protein that BP1001 blocks is called Grb-2. The response of the leukemia to this treatment will also be studied. In addition, the time needed for the body to process this drug will be evaluated.
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a signaling adaptor protein with two EH domains that interacts with proteins that participate in signaling, endocytosis and cytoskeletal changes. The encoded protein has been found in association with intersectin 1 and Src homology 3-domain growth factor receptor-bound 2-like (endophilin) interacting protein 1 when intersectin 1 was isolated from clathrin-coated pits. The encoded protein has also been shown to interact with amphiphysin, a cytoplasmic protein at the surface of synaptic vesicles. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2014 ...
We have shown that THEMIS is required to enact a TCR‐induced negative feedback mechanism that modulates signal transmission. Previous work revealed similar TCR‐induced negative feedback devices originating from the LAT:SLP‐76 complex, which were mediated by the adaptors DOK‐1/DOK‐2 or the kinase HPK1 (Dong et al, 2006; Di Bartolo et al, 2007). However, in contrast to THEMIS KO mice, HPK1 KO or DOK‐1/DOK‐2 double KO showed no detectable defect of T‐cell development (Shui et al, 2007; Yasuda et al, 2007). Thus, THEMIS is part of an as yet unique TCR‐induced regulatory mechanism critical to drive T‐cell development (Fu et al, 2013). We found that THEMIS is constitutively associated with SHP1 and SHP2 through the adaptor GRB2. THEMIS knock‐down in human T cells and Jurkat 1G4‐CD8 cells increased CD3‐ζ phosphorylation and downstream activation events. Because TCR ligation induces recruitment of THEMIS, via GRB2, onto LAT (Paster et al, 2013), we infer that THEMIS allows ...
TITLE: GCN GRB OBSERVATION REPORT NUMBER: 2156 SUBJECT: GRB030329: 444 AAVSO Measurements DATE: 03/04/20 03:21:34 GMT FROM: AAVSO GRB Network at AAVSO ...
Looking for online definition of growth factor receptor-bound protein 7 in the Medical Dictionary? growth factor receptor-bound protein 7 explanation free. What is growth factor receptor-bound protein 7? Meaning of growth factor receptor-bound protein 7 medical term. What does growth factor receptor-bound protein 7 mean?
Increasing β-cell mass is one of the mechanisms by which glucose homeostasis is maintained in vivo in response to physiological (i.e., growth and gestation) and pathophysiological (i.e., obesity and insulin resistance) stimuli. Unlike other terminally differentiated cell types, pancreatic β-cells retain their ability to proliferate under both physiological and pathophysiological conditions (3). In the progression of diabetes, insulin secretion is increased, and a large amount of the increase in the first stage of this compensation process is due to increased β-cell mass, which is mainly achieved through an increase in β-cell number (24).. The gene encoding for Grb10 is imprinted in mammalian cells, and its expression is defined by its parental origins (25). The maternal allele determines Grb10 expression in all tissues except the brain, and the paternal allele determines Grb10 expression in the brain. Grb10 is expressed in insulin target tissues such as fat and muscle in vivo. The unique ...
An adaptor protein (growth factor receptor bound protein 2, 217 aa), the mammalian homologue of Caenorhabditis elegans Sem-5 and Drosophila Drk that links the cytoplasmic domain of growth factor receptors to downstream elements of the signalling pathway through its SH2 and SH3 domains. The SH2 domain binds autophosphorylated residues on the growth factor receptors cytoplasmic tail and the SH3 domain binds nucleotide exchange factors such as sos1. Grb2-associated binder-1 (gab-1, 694 aa) binds to Grb-2 and has homology with IRS-1 (insulin receptor substrate-1). It is a substrate for the EGF receptor and may integrate signals from different receptors into the control of cellular responses. Grb2-related adaptor protein-1 (GRAP1; 217 aa) interacts in vitro with c-kit (stem cell factor receptor) and the erythropoietin receptor, linking them to the ras signalling pathway. Grb2-related adaptor protein-2 (GRAP2, GADS, 330 aa) is another of the Grb2/Sem5/Drk family and reportedly involved in ...
Original model: BIOMD0000000048 The epidermal growth factor receptor (EGFR) is part of the protein-tyrosine kinase receptor family. It regulates cell growth, survival, proliferation and differentiation. Epidermal growth factor binds to the EGFR, and facilitates receptor dimerization and rapid activation of its intrinsic tyrosine kinase, followed by autophosphorylation of multiple tyrosine residues in the cytoplasmic receptor domain. This tyrosine phosphorylation of EGFR triggers a number of biochemical reactions involving various protein domains (as an example, see Figure 1 for the targets involved in tumor cells [1]). Kholodenko et al developed the first detailed kinetic model of EGF receptor function [2] (a similar model was created in parallel by Bhalla and Iyengar [3]). The authors focus on the activation of the growth factor receptor-binding protein 2 (Grb2), Src homology and collagen domain protein (Shc) and phosholipase C-γ (PLC-γ). Pathways involving Grb2 and Shc lead to the activation ...
Defects in insulin secretion and reduction in β-cell mass are associated with type 2 diabetes in humans and understanding the basis for these dysfunctions may reveal strategies for diabetes therapy. In this study, we show that pancreas-specific knockout of growth factor receptor-binding protein 10 (Grb10), which is highly expressed in pancreas and islets, leads to elevated insulin/IGF-1 signaling in islets, enhanced β-cell mass and insulin content, and increased insulin secretion in mice. Pancreas-specific disruption of Grb10 expression also improved glucose tolerance in mice fed with a high-fat diet and protected mice from streptozotocin-induced β-cell apoptosis and body weight loss. Our study has identified Grb10 as an important regulator of β-cell proliferation and demonstrated that reducing the expression level of Grb10 could provide a novel means to increase β-cell mass and reduce β-cell apoptosis. This is critical for effective therapeutic treatment of both type 1 and 2 diabetes. ...
2506 The tumor suppressing ability of p27Kip1 (Kinase Inhibitory Protein 1) is commonly assigned to its cyclin dependent kinase (CDK) inhibitory function. However, we recently identified a separable and distinct role for p27 regulating Growth Factor Receptor-Bound Protein 2 (GRB2). GRB2 participates in key signaling pathways often hyperactivated in human cancers. Conversely, p27 function is often disrupted in human cancers, and loss of p27 function may contribute to tumorigenesis by compromising GRB2-mediated signal transduction. We now show p27 regulates GRB2 in untransformed breast epithelial cells. This pathway is temporally disrupted in breast cancer cells, which contain excess cyclin D1-CDK4 which sequesters p27 destined to target GRB2. Our results describe the first example of transformed cells compromising a p27 function other than CDK inhibition, and thus provide an alternative explanation of why p27 is frequently disrupted in human cancers. ...
Bio-Path Holdings, Inc. is a clinical and preclinical stage oncology focused antisense drug development company. The Company utilizes a technology that achieves systemic delivery for target specific protein inhibition for any gene product that is over-expressed in disease. Its drug delivery and antisense technology, DNAbilize, is a platform that uses P-ethoxy, a deoxyribonucleic acid backbone modification. Its lead drug candidate, Liposomal Grb2 (BP1001), targets the protein Growth factor receptor-bound protein 2 (Grb2). Its other liposome delivered antisense drug candidate, Liposomal Bcl2 (BP1002), targets the protein B-cell lymphoma 2 (Bcl2). BP1001 is in Phase II clinical trials for acute myeloid leukemia, and for blast phase and accelerated phase chronic myelogenous leukemia. BP1002 is intended to target the lymphoma and certain solid tumor markets. BP1001 is also in preclinical studies for solid tumors, including triple negative breast cancer and inflammatory breast cancer.. ...
The role of Shc-GRB2-Sos and Ras in signal transduction by Gq-coupled receptors, such as the AT1 receptor, is unclear. Importantly, tyrosine phosphorylation of Shc61 82 106 and activation of Ras by angiotensin II were recently demonstrated.107 Tyrosine phosphorylation of a linker protein called Shc appears to be an important mechanism used by all G protein-coupled receptors on the basis of studies to date.108 For Gi-coupled receptors, a pathway for activation of Ras and ERK1/2 has been proposed (Fig 2⇑)106 107 108 in which release of G-protein βγ subunits from G protein-coupled receptors stimulates downstream events leading to tyrosine phosphorylation of Shc.109 c-Src has been proposed as a likely candidate.108 110 111 Additional signal mediators that may be required include PI 3-K and a protein tyrosine phosphatase.108 Once Shc is tyrosine-phosphorylated, it now binds GRB2 via SH2 domain interactions (Fig 2⇑). GRB2 also binds to the guanine nucleotide exchange factor Sos via SH3 ...
Purified Recombinant Mouse Grb7 Protein, His-tagged from Creative Biomart. Recombinant Mouse Grb7 Protein, His-tagged can be used for research.
Granzyme B (GrB) è una proteasi di tipo serinico espressa dai linfociti citotossici (linfociti T e cellule NK), che in presenza di perforina (Pf), induce apoptosi nelle cellule bersaglio quali cellule infettate e cellule tumorali. Recentemente, è stato dimostrato che GrB è espressa, spesso in assenza di Pf, anche in cellule non-linfoidi; tuttavia il ruolo di GrB in queste cellule non è stato ancora definito. Lobbiettivo della mia ricerca è stato quello di indagare: - lespressione di GrB e Pf in linee cellulari e in tessuti di carcinoma della vescica, mediante RT-PCR, Western Blot, ELISA, immunofluorescenza e immunoistochimica. - la funzione di GrB in vitro mediante saggi di attività enzimatica e saggi di invasione cellulare, in presenza o in assenza di silenziamento genico di GrB. I risultati di questo studio hanno rivelato lespressione di GrB, in assenza di Pf, in cellule e tessuti di carcinoma uroteliale (UC). Differenze significative sono state riscontrate tra lespressione di GrB e ...
Recombinant GRB2-Related Adaptor Protein (GRAP) Protein (Myc-DYKDDDDK Tag). Species: Human. Source: HEK-293 Cells. Order product ABIN2722222.
These |i|Grb2|/i| floxed mice may be useful for studying the effect of GRB2-dependant signal transduction on lymphocyte differentiation and immune response.
GRB2 antibody detects GRB2 protein by Western blot analysis.A. 30 μg THP-1 whole cell lysate/extract12 % SDS-PAGEGRB2 antibody (GTX101176) dilution: 1: ...
Hop on to get the meaning of Gab2 acronym / slang / Abbreviation. The Medical & Science Acronym / Slang Gab2 means... AcronymsAndSlang. The Gab2 acronym/abbreviation definition. The Gab2 meaning is Grb2-associated binder 2. The definition of Gab2 by AcronymAndSlang.com
SGIP1 (SH3 domain GRB2 like endophilin interacting protein 1), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
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ヤギ・ポリクローナル抗体 ab2234 交差種: Ms,Rat,Hu,Pig 適用: WB,ELISA,IHC-P…GRB2抗体一覧…画像、プロトコール、文献などWeb上の情報が満載のアブカムの Antibody 製品。国内在庫と品質保証制度も充実。
To identify receptor-associated proteins that may contribute to the specificity of insulin and IGF-I signaling responses, a mouse embryo library was screened using the yeast two-hybrid system. Multiple receptor-interactive clones encoding the SH2 domain of the adapter protein Grb10 were isolated. Subsequent cloning of the full-length Grb10 sequence from a mouse fat cDNA library defined a previously unknown Grb10 variant, that appears to be the predominant isoform in mouse tissues. Receptor-deficient R- cells (fibroblasts from mice with homologous disruption of the IGF-I receptor gene) and transfected R- cells expressing either insulin receptors (R-IR cells) or IGF-I receptors (R+ cells) were used to investigate the specificity of Grb10 interaction with the two related receptors. Hormone-activated insulin receptors in R-IR cells coprecipitated with three species, all recognized as Grb10 isoforms by specific Grb10 antibody. Under the same conditions, Grb10 was essentially undetectable in IGF-I ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
H. Krimm (GSFC/USRA), L. Barbier (GSFC), S. Barthelmy (GSFC), J. Cannizzo (GSFC-UMBC), J. Cummings (GSFC/NRC), E. Fenimore (LANL), N. Gehrels (GSFC), D. Hullinger (GSFC/UMD), C. Markwardt (GSFC/UMD), D. Palmer (LANL), A. Parsons (GSFC), T. Sakamoto (GSFC/NRC), G. Sato (ISAS), M. Tashiro (Saitama U.), J. Tueller (GSFC) on behalf of the Swift-BAT team: Using the data set from T-299.0 to T+183.0 sec from the recent telemetry downlink, we report further analysis of BAT GRB 060203 (trigger #180151) (Retter et al., 4641, Burrows et al., GCN 4644, Cummings et al., GCN 4649). The BAT ground-calculated position is (RA,Dec) = 103.502, 71.838 deg {06h 54m 0.5s,+71d 50 15.9} (J2000) +- 1.9 arcmin, (radius, sys+stat, 90% containment). The partial coding was 50%. Based on the event data that we have, the mask-weighted light curve shows a single broad peak lasting from T-20 to T+65 seconds. T90 (15-350 keV) is 60 +- 10 sec (estimated error including systematics). There is no evidence in the rate data for ...
Portland, Ore. - Oregon Health & Science University Knight Cancer Institute researchers found that the GRB7 gene drives an aggressive form of breast cancer and acts independently of the HER-2 gene, known to be a stimulator of breast cancer growth. Isolating the role of this gene could ultimately help fine-tune a patients treatment and enable physicians to provide a more accurate prognosis. The study, published online this month by Breast Cancer Research and Treatment, established that levels of GRB7, or growth factor receptor bound protein seven, are important on their own as a marker for aggressive breast cancer. Previously it was understood that patients whose breast cancer tumors tested positive for high levels of HER-2, the protein human epidermal growth factor receptor-2, tended to have a more aggressive form of the disease than patients whose tumors did not have elevated levels of this protein. However, OHSU Knight Cancer Institute researchers found that the protein driving this ...
Scientists may soon help people grow strong muscles without needing to hit the weight room. As reported in The FASEB Journal, researchers discovered that by blocking the function of the protein Grb10 in mice in the womb, they developed as more muscular than their normal counterparts. This presents important implications for a range of conditions that are worsened by, or cause muscle wasting, such as injury, muscular dystrophy, and Type 2 diabetes.
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Insulin receptor signaling acutely stimulates GTP loading of p21ras, apparently by mobilizing complexes of Grb2 and the guanine nucleotide exchangers Son-of-sevenless (Sos) 1 and 2 to associate with tyrosine-phosphorylated proteins in the plasma membrane. Here we show that in 32P-labeled 3T3-L1 adipocytes the elevated cellular concentrations of [32P]GTP-bound p21ras in response to insulin return to near basal levels after 20-30 min of hormone stimulation, while insulin receptors remain activated. Lysates of such desensitized cells were quantitatively immunoprecipitated with an antiserum recognizing both Sos1 and Sos2 proteins or a specific anti-Sos2 antiserum. Immunoblot analysis of these precipitates revealed that insulin causes a marked hyperphosphorylation of Sos1 and a 50% decrease in Grb2 associated with Sos proteins under these conditions. Similarly, anti-Grb2 immunoprecipitates of such lysates revealed the presence of decreased Sos1 protein due to insulin action. The disassembly of Grb2 from Sos
This gene encodes three main isoforms that differ in activities and subcellular location. While all three are adapter proteins in signal transduction pathways, the longest (p66Shc) may be involved in regulating life span and the effects of reactive oxygen species. The other two isoforms, p52Shc and p46Shc, link activated receptor tyrosine kinases to the Ras pathway by recruitment of the GRB2/SOS complex. p66Shc is not involved in Ras activation. Unlike the other two isoforms, p46Shc is targeted to the mitochondrial matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011] ...
Myc-DDK-tagged ORF clone of Homo sapiens GRB10 interacting GYF protein 2 (GIGYF2), transcript variant 1 as transfection-ready DNA - 10 µg - OriGene - cdna clones
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14 January 2015: Imprinted genes are monoallelic expressed in a parent-of-origin dependent manner (Jirtle and Weidman 2007).The conflict theory of genomic imprinting predicts that maternally expressed genes are antigrowth while paternally expressed genes are progrowth (Haig and Graham 1991). The first two genes experimentally identified to be imprinted, the maternally expressed Igf2r (Barlow et al. 1991) and the paternally expressed Igf2 (DeChiara et al. 1991), were shown over two decades ago to adhere to this prediction. A second set of oppositely imprinted, fetal growth antagonistic genes has now been identified, the maternally expressed Grb10 and the paternally expressed Dlk1 (Madon-Simon et al. 2014). Grb10 encodes for an intracellular signaling adaptor protein that restricts fetal growth and promotes fat deposition. In contrast, Dlk1 encodes for a ligand that promotes fetal growth and restricts fat deposition. Deregulation of DLK1 expression by a single point mutation also results in the ...
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Breast cancer is widely and effectively treated with endocrine treatment. However, in many cases the tumours will eventually progress into
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GRB2-related adapter protein is a protein that in humans is encoded by the GRAP gene. This gene encodes a member of the GRB2/ ... "Entrez Gene: GRAP GRB2-related adaptor protein". Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE (Jan 1998). "LAT ... "Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients ... Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (May 1996). "Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine ...
"Networks of interaction of p120cbl and p130cas with Crk and Grb2 adaptor proteins". Oncogene. 12 (12): 2491-8. PMID 8700507. ... of adaptor proteins which is characterized by the presence of multiple conserved motifs for protein-protein interactions, and ... p130Cas/BCAR1 belongs to the Cas family of adaptor proteins and can act as a docking protein for several signalling partners. ... Brinkman A, van der Flier S, Kok EM, Dorssers LC (Feb 2000). "BCAR1, a human homologue of the adapter protein p130Cas, and ...
Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein". The Journal of Biological Chemistry ... is a signaling adapter protein that in humans is encoded by the IRS-1 gene. It is a 131 kDa protein with amino acid sequence of ... Dearth RK, Cui X, Kim HJ, Hadsell DL, Lee AV (March 2007). "Oncogenic transformation by the signaling adaptor proteins insulin ... Dearth RK, Cui X, Kim HJ, Hadsell DL, Lee AV (March 2007). "Oncogenic transformation by the signaling adaptor proteins insulin ...
The adaptor protein Grb2 forms a complex with Sos by the Grb2 SH3 domain. Grb2 (or the Grb2/Sos complex) is recruited to the ... Whereas the interaction between Grb2 and PDGFR occurs through interaction with the SHP2 protein, Grb2 instead binds to ... another adaptor protein that forms a complex with many receptors via its PTB domain. Once activated, Ras interacts with several ... Similarly to other SH2 domain-containing proteins, PI-3 kinase forms a complex with PY sites on activated receptors. The main ...
"The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins". Oncogene. 9 (6): 1661-8. PMID ... "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): ... "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7". J. Biol. ... resulting in the juxtaposition of the C-terminal region of the RET protein with an N-terminal portion of another protein, can ...
MacDonald JI, Gryz EA, Kubu CJ, Verdi JM, Meakin SO (June 2000). "Direct binding of the signaling adapter protein Grb2 to the ... June 1994). "The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins". Oncogene. 9 (6): ... The levels of distinct proteins can be regulated by the "ubiquitin/proteasome" system. In this system, a small (7-8 kd)protein ... Geetha T, Wooten MW (February 2003). "Association of the atypical protein kinase C-interacting protein p62/ZIP with nerve ...
One of the seminal findings in this work was his laboratory's cloning of Grb2 and other Adaptor proteins. Another is the lab's ...
... involvement of the Grb2, p130cas, and Nck adaptor proteins". Molecular and Cellular Biology. 17 (3): 1702-13. doi:10.1128/mcb. ... PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, is encoded by ... The encoded protein is a member of the FAK subfamily of protein tyrosine kinases that included PYK2, but lacks significant ... Lineage for Protein: Focal adhesion kinase 1 Q00944 "Entrez Gene: PTK2 PTK2 protein tyrosine kinase 2". Guan JL, Shalloway D ( ...
GRB2-related adapter protein 2 also known as GRB2-related adaptor downstream of Shc (GADS) is a 37 kDa protein that in humans ... This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein ( ... Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 ... "Entrez Gene: GRAP2 GRB2-related adaptor protein 2". Xia C, Bao Z, Tabassam F, Ma W, Qiu M, Hua S, Liu M (Jul 2000). "GCIP, a ...
Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein". J. Biol. Chem. 275 (6): 4283-9. doi ... Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the ... The pTyr loop and Tyr46 residue are located on the surface of the protein, and thus help to determine the depth a substrate can ... PTP1B was first isolated from a human placental protein extract, but it is expressed in many tissues. PTP1B is localized to the ...
An amide ring is employed in the specificity of the adaptor protein GRB2 for a particular asparagine within proteins it binds. ... Motivated Proteins: [1]; PDBeMotif: [2]. v t e Leader, DP; Milner-White (2009). "Motivated Proteins: A web application for ... GRB2 binds strongly to the pentapeptide EYINQ (when the tyrosine is phosphorylated); in such structures a 9-atom amide ring ... Amide Rings are small motifs in proteins and polypeptides. They consist of 9-atom or 11-atom rings formed by two CO...HN ...
Ellis JH, Ashman C, Burden MN, Kilpatrick KE, Morse MA, Hamblin PA (June 2000). "GRID: a novel Grb-2-related adapter protein ... Koehler JA, Moran MF (May 2001). "RACK1, a protein kinase C scaffolding protein, interacts with the PH domain of p120GAP". ... RACK1 was originally isolated and identified as an intracellular protein receptor for protein kinase C, noting the significant ... RAS p21 protein activator 1, ST7, STAT1, Src, and Tyrosine kinase 2. Eukaryotic small ribosomal subunit (40S) Protein kinase C ...
... a novel Grb-2-related adapter protein that interacts with the activated T cell costimulatory receptor CD28". J. Immunol. 164 ( ... Okkenhaug K, Rottapel R (August 1998). "Grb2 forms an inducible protein complex with CD28 through a Src homology 3 domain- ... The N172 residue (as part of the YMNM) is important for the binding of Grb2 and Gads and seems to be able to induce IL-2 mRNA ... However, mutation of the final amino acid of the motif, M173, which is unable to bind PI3K but is able to bind Grb2 and Gads, ...
... and cytoplasmic forms of protein tyrosine phosphatase epsilon physically associate with the adaptor molecule Grb2". Oncogene. ... The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling ... "Protein tyrosine phosphatase epsilon inhibits signaling by mitogen-activated protein kinases". Mol. Cancer Res. 1 (7): 541-50. ... "Entrez Gene: PTPRE protein tyrosine phosphatase, receptor type, E". Peretz A, Gil-Henn H, Sobko A, Shinder V, Attali B, Elson A ...
For example, SOS1, the Ras GEF in the MAPK/ERK pathway, is recruited by the adaptor protein GRB2 in response to EGF receptor ... GEFs are multi-domain proteins and interact with other proteins inside the cell through these domains. Adaptor proteins can ... This 200 amino acid region is homologous to the yeast Sec7p protein. GEFs are often recruited by adaptor proteins in response ... SOS1 binds GRB2 at the plasma membrane after EGF receptor activation. SOS1 activates the small G protein Ras. eIF-2b is a ...
Grb2 adapter protein, and Sos nucleotide exchange factor". Cell. 73 (3): 611-620. doi:10.1016/0092-8674(93)90146-H. PMID ... and are often specific to a single protein or class of proteins with which they interact. Nucleoside-diphosphate kinase Guanine ... of nucleoside diphosphates for nucleoside triphosphates bound to other proteins. Many cellular proteins cleave (hydrolyze) ... These changes in turn affect the structural, enzymatic, or signalling properties of the protein. Nucleotide exchange factors ...
Signal transducing adaptor proteins CDC24 Cdc25 PI3 kinase Phospholipase Ras GTPase-activating protein Vav proto-oncogene GRB2 ... The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually ... Examples are the C-terminal SH3 domains of adaptor proteins like Grb2 and Mona (a.k.a. Gads, Grap2, Grf40, GrpL etc.). Other ... Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the ...
Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J (Mar 1994). "A complex of Grb2 adaptor protein, Sos exchange ... This protein is a member of the annexin family. Members of this calcium-dependent phospholipid-binding protein family play a ... Becker T, Weber K, Johnsson N (Dec 1990). "Protein-protein recognition via short amphiphilic helices; a mutational analysis of ... It is a calcium-dependent phospholipid-binding protein whose function is to help organize exocytosis of intracellular proteins ...
"SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and ... Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J (March 1994). "A complex of Grb2 adaptor protein, Sos exchange ... Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (1996). "Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine ... Park RK, Izadi KD, Deo YM, Durden DL (September 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI ...
... coupling to the adaptor protein GRB2". Arch. Biochem. Biophys. 345 (1): 103-10. doi:10.1006/abbi.1997.0245. PMID 9281317. Nel ... Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (February 1996). "A Grb2-associated docking protein in EGF- and ... BAG3 balances protein synthesis and protein degradation under mechanical stress. PLCG1 has been shown to interact with: FGFR1, ... Suzuki H, Fukunishi Y, Kagawa I, Saito R, Oda H, Endo T, Kondo S, Bono H, Okazaki Y, Hayashizaki Y (Oct 2001). "Protein-protein ...
... coupling to the adaptor protein GRB2". Archives of Biochemistry and Biophysics. 345 (1): 103-10. doi:10.1006/abbi.1997.0245. ... Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (February 1996). "A Grb2-associated docking protein in EGF- and ... Oneyama C, Nakano H, Sharma SV (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction ... Grb2, HER2/neu, IRS2, ITK, KHDRBS1, Linker of activated T cells, Lymphocyte cytosolic protein 2, PDGFRA, PLD2, RHOA, SOS1, TUB ...
... a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo". EMBO J. 13 (13): 3020-32. doi:10.1002/j.1460-2075.1994. ... a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo". EMBO J. 13 (13): 3020-32. doi:10.1002/j.1460-2075.1994. ... den Hertog J, Hunter T (1996). "Tight association of GRB2 with receptor protein-tyrosine phosphatase alpha is mediated by the ... The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling ...
"SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins". Cellular ... "SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins". Cellular ... SH3 domain-containing kinase-binding protein 1 (synonyms - CIN85, in rodents - Ruk) is an adaptor protein that in humans is ... Watanabe S, Take H, Takeda K, Yu ZX, Iwata N, Kajigaya S (November 2000). "Characterization of the CIN85 adaptor protein and ...
"SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins". Cell. ... "The adapter type protein CMS/CD2AP binds to the proto-oncogenic protein c-Cbl through a tyrosine phosphorylation-regulated Src ... is a mammalian gene encoding the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ... Park RK, Izadi KD, Deo YM, Durden DL (September 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI ...
An adapter protein such as Grb2 will bind to phosphate-tyrosine residues under the influence of receptor protein kinases. This ... Protein tyrosine kinase plays a role in this task, too. A protein tyrosine kinase called pp125 is likely at hand in the ... This protein tyrosine kinase is up to about 70% unique compared to some other protein tyrosine kinases, a figure that is unlike ... The protein tyrosine kinase pp125 is one of the major phosphotyrosine-containing proteins in unaffected (untransformed) avian ...
"Chromosome locations of genes encoding human signal transduction adapter proteins, Nck (NCK), Shc (SHC1), and Grb2 (GRB2)". ... The Nck (non-catalytic region of tyrosine kinase adaptor protein 1) belongs to the adaptor family of proteins. The nck gene was ... "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... "The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck". J. Biol. Chem. 273 (33): ...
"Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living ... "Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J (March 1994). "A complex of Grb2 adaptor protein, Sos exchange ... a novel Src homology2/3-containing adaptor protein that interacts with the LIM-only protein PINCH and components of growth ...
... domain that is contained in the adaptor protein families Crk, Grb2, and Nck. These adaptor proteins then couple to enzymes to ... GRB2-associated-binding protein 2 also known as GAB2 is a protein that in humans is encoded by the GAB2 gene. GAB2 is a docking ... The interaction between GAB2 and Grb2 at the cell membrane recruits another adaptor protein, the Src homology domain-containing ... "The lymphoid protein tyrosine phosphatase Lyp interacts with the adaptor molecule Grb2 and functions as a negative regulator of ...
"Wiskott-Aldrich syndrome protein is associated with the adapter protein Grb2 and the epidermal growth factor receptor in living ... "The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck". The Journal of Biological ... protein binding. • identical protein binding. • actin binding. • protein kinase binding. • small GTPase binding. • Rac GTPase ... The Wiskott-Aldrich Syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system. In the ...
Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein ... "GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin- ... protein binding. • thioesterase binding. • protein kinase binding. • nucleotide binding. • GTP binding. • identical protein ... "Protein Data Bank in Europe. EMBL-EBI. Retrieved 2016-04-22.. *^ "CDC42 (cell division cycle 42 (GTP binding protein, 25kDa))" ...
Sato, K; Kimoto M, Kakumoto M, Horiuchi D, Iwasaki T, Tokmakov A A, Fukami Y (September 2000). "Adaptor protein Shc undergoes ... Grb2,[8][18] Beta-3 adrenergički receptor,[19] Kinaza beta adrenergičkog receptora,[8] Receptor epidermalnog faktora rasta,[9][ ... "Identification of Src as a novel atypical protein kinase C-interacting protein". Mol. Cell Biol. Res. Commun. (UNITED STATES) 2 ... "A human protein-protein interaction network: a resource for annotating the proteome". Cell (United States) 122 (6): 957-68. ...
This adaptor protein is called the Fcγ subunit and, like FcγRIIA, contains the two YXXL sequences that are characteristic of an ... Negative signaling through SHIP appears to inhibit the Ras pathway through SH2 domain competition with Grb2 and Shc and may ... An Fc receptor is a protein found on the surface of certain cells - including, among others, B lymphocytes, follicular ... Activated eosinophils release preformed mediators such as major basic protein, and enzymes such as peroxidase, against which ...
Tirozin-kinaza, Fyn, fosforilizira Grb-2-vezani veznoliki protein 2 (Gab2) koji se veže na fosfoinozitid 3-kinazu, koja ... Važan proteinski adapter aktivira Syk-fosforilaciju, koja je korak za aktivaciju T-ćelija (LAT). One su važne jer se mogu ... Aktivira protein-kinazu C Protein-kinaza C. Aktivira pokretanje fosforilacije granula miozinskog lahkog lanca koje rastavljaju ... Grb-2-vezani vezoliki protein. Veže fosfoinozitid 3-kinazu Fosfoinozitid 3-kinaza. ...
Jahn T, Seipel P, Urschel S, Peschel C, Duyster J (2002). „Role for the adaptor protein Grb10 in the activation of Akt". Mol. ... The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells". J. Biol. Chem. 269 (40): ... Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (1996). „Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine ... Gueller S, Gery S, Nowak V, Liu L, Serve H, Koeffler HP (2008). „Adaptor protein Lnk associates with Tyr(568) in c-Kit". ...
... signal transducing adaptor proteins. JAK-STAT. *see JAK-STAT signaling pathway. Growth factor receptor-bound protein. *GRB2 ... In molecular biology caveolins are a family of integral membrane proteins that are the principal components of caveolae ... The caveolin gene family has three members in vertebrates: CAV1, CAV2, and CAV3, coding for the proteins caveolin-1, caveolin-2 ... All three members are membrane proteins with similar structure. Caveolin forms oligomers and associates with cholesterol and ...
... "p130CAS forms a signaling complex with the adapter protein CRKL in hematopoietic cells transformed by the BCR/ABL oncogene". J ... MeSH protein, human PTK2 protein, human. *"Breaking down cancer's wall of resistance", by DR Nick Peel, Cancer Research UK, ... PTK2 proteinska tirozinska kinaza 2 (PTK2, Fokalna adheziona kinaza, FAK), protein je koji je kod ljudi kodiran PTK2 genom.[2] ... "The GIT family of proteins forms multimers and associates with the presynaptic cytomatrix protein Piccolo". J. Biol. Chem. 278 ...
Grb2) along with a docking protein called Grb2-associated Binder-1 (GAB1).[7] Subsequently, phosphatidylinositol-3 kinase (PI3K ... In this pathway, recruitment of a guanine nucleotide exchange factor by the adaptor and docking proteins leads to activation of ... The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf.[7] Raf in turn activates ... Survival and PCD mechanisms are mediated through adaptor protein binding to the death domain of the p75NTR cytoplasmic tail. ...
Role for the adaptor protein Grb10 in the activation of Akt. », Mol. Cell. Biol., vol. 22, no 4,‎ février 2002. , p. 979-91 ( ... The ubiquitously expressed Syp phosphatase interacts with c-kit and Grb2 in hematopoietic cells. », J. Biol. Chem., vol. 269, n ... Adaptor protein Lnk associates with Tyr(568) in c-Kit. », Biochem. J., vol. 415, no 2,‎ octobre 2008. , p. 241-5 (PMID 18588518 ... Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway. », J. Biol. Chem., vol. 271, no ...
... implications for function as adapter proteins". FEBS Lett. 368 (1): 55-8. doi:10.1016/0014-5793(95)00598-4. PMID 7615088.. ... protein binding. • MHC class II protein complex binding. • protein heterodimerization activity. • enzyme binding. • poly(A) RNA ... 14-3-3 protein epsilon is a protein that in humans is encoded by the YWHAE gene.[5] ... identical protein binding. • macromolecular complex binding. • cadherin binding. • scaffold protein binding. Cellular component ...
Ren R, Ye ZS, Baltimore D (April 1994). "Abl protein-tyrosine kinase selects the Crk adapter as a substrate using SH3-binding ... GRB2, MDM2, NCK1, NEDD9, NTRK1, P73, PAG1, PAK2, PSTPIP1, RAD9A, RAD51, RB1, RFX1, RYBP, SHC1, SORBS2, SPTA1, SPTAN1, TERF1, ... Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY, Duyster J (August 1998). "The SH2-containing adapter protein GRB10 ... Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene (previous symbol ABL ...
Alpha-1-syntrophin is a protein that in humans is encoded by the SNTA1 gene. Alpha-1 syntrophin is a signal transducing adaptor ... Oak SA, Russo K, Petrucci TC, Jarrett HW (2001). "Mouse alpha1-syntrophin binding to Grb2: further evidence of a role for ... The protein encoded by this gene is a peripheral membrane protein found associated with dystrophin and dystrophin-related ... Fernández-Larrea J, Merlos-Suárez A, Ureña JM, Baselga J, Arribas J (1999). "A role for a PDZ protein in the early secretory ...
"Adaptor proteins Grb2 and Crk couple Pyk2 with activation of specific mitogen-activated protein kinase cascades". J. Biol. Chem ... Adapter molecule crk is a member of an adapter protein family that binds to several tyrosine-phosphorylated proteins. This ... Adapter molecule crk also known as proto-oncogene c-Crk is a protein that in humans is encoded by the CRK gene. The CRK protein ... related protein kinases HPK1 and KHS are candidates for highly selective signal transducers of Crk family adapter proteins". ...
Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to ... "The Dok-3/Grb2 adaptor module promotes inducible association of the lipid phosphatase SHIP with the BCR in a coreceptor- ... pathways independently on its catalytic activity by serving as a bridge for other proteins thereby regulate protein-protein ... Overall, the protein functions as a negative regulator of cell proliferation and survival. Nevertheless, SHIP1 may also bind to ...
"Identification of Grb2 as a novel binding partner of the signaling lymphocytic activation molecule-associated protein binding ... Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (1996). "A "double adaptor" method for improved shotgun library ... LY9+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from ... T-lymphocyte surface antigen Ly-9 is a protein that in humans is encoded by the LY9 gene. LY9 has also recently been designated ...
Pandey A, Duan H, Dixit VM (1995). "Characterization of a novel Src-like adapter protein that associates with the Eck receptor ... EPH receptor A2 has been shown to interact with: ACP1 Grb2, PIK3R1, and SHC1. GRCh38: Ensembl release 89: ENSG00000142627 - ... an epithelial cell receptor protein-tyrosine kinase in the eph/elk family of protein kinases". Mol. Cell. Biol. 10 (12): 6316- ... EPH receptor A2 (ephrin type-A receptor 2) is a protein that in humans is encoded by the EPHA2 gene. This gene belongs to the ...
First, the protein Grb2 binds the P-Tyr residue of IRS-1 in its SH2 domain. Grb2 is then able to bind SOS, which in turn ... These changes facilitate the recruitment of specific adapter proteins such as the insulin receptor substrate proteins (IRS) in ... Kotani K, Wilden P, Pillay TS (October 1998). "SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts ... This protein then begins a phosphorylation cascade, culminating in the activation of mitogen-activated protein kinase (MAPK), ...
This allows the adaptor molecule Fas-associated death domain (FADD) to bind the death domain of Fas through its own death ... Fas ligand (FasL or CD95L or CD178) is a type-II transmembrane protein that belongs to the tumor necrosis factor (TNF) family. ... Fas ligand has been shown to interact with: CASP8, EZR, FADD, FNBP1, FYN, FAS, Grb2, PACSIN2, and TNFRSF6B. FAF1 GRCh38: ... In most cell types, caspase-8 catalyzes the cleavage of the pro-apoptotic BH3-only protein Bid into its truncated form, tBid. ...
"Induced direct binding of the adapter protein Nck to the GTPase-activating protein-associated protein p62 by epidermal growth ... PDGFRB has been shown to interact with: CRK, Caveolin 1, Grb2, NCK1, NCK2, PDGFR-α, PTPN11, RAS p21 protein activator 1, SHC1 ... yield a PDGFRB-ETV6 fused gene that encodes a fusion protein, PDGFRB-ETV6. This chimeric protein, unlike the PDGFRB protein: a ... a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". J. Biol. ...
2007). "Dok-3 sequesters Grb2 and inhibits the Ras-Erk pathway downstream of protein-tyrosine kinases". Genes Cells. 11 (2): ... Lemay S, Davidson D, Latour S, Veillette A (Apr 2000). "Dok-3, a Novel Adapter Molecule Involved in the Negative Regulation of ... Docking protein 3 is a protein that in humans is encoded by the DOK3 gene. GRCh38: Ensembl release 89: ENSG00000146094 - ... "Entrez Gene: DOK3 docking protein 3". Cong F, Yuan B, Goff SP (2000). "Characterization of a Novel Member of the DOK Family ...
Sugiyama Y, Tomoda K, Tanaka T, Arata Y, Yoneda-Kato N, Kato J (2001). "Direct binding of the signal-transducing adaptor Grb2 ... It encodes a protein which belongs to the Cip/Kip family of cyclin dependent kinase (Cdk) inhibitor proteins. The encoded ... Degradation of the p27 protein occurs as cells exit quiescence and enter G1. Protein levels continue to fall rapidly as the ... protein. Increased levels of the p27Kip1 protein typically cause cells to arrest in the G1 phase of the cell cycle. Likewise, ...
"The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): ... "Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells". ... Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is ... "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): ...
... and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. The protein encoded by this gene facilitates macrophage ... GRB2 associated binding protein 3 is a protein that in humans is encoded by the GAB3 gene. This gene is a member of the GRB2- ... associated binding protein gene family. These proteins are scaffolding/docking proteins that are involved in several growth ... "GAB3 GRB2 associated binding protein 3 [ Homo sapiens (human) ]". National Center for Biotechnology Information. Retrieved 2019 ...
... an adaptor protein that is developmentally regulated during cardiac myocyte differentiation". The Journal of Biological ... NCKIPSD has been shown to interact with Grb2 and NCK1. GRCh38: Ensembl release 89: ENSG00000213672 - Ensembl, May 2017 "Human ... NCK-interacting protein with SH3 domain is a protein that in humans is encoded by the NCKIPSD gene. The protein encoded by this ... "Entrez Gene: NCKIPSD NCK interacting protein with SH3 domain". Satoh S, Tominaga T (October 2001). "mDia-interacting protein ...
The Grb2/Mek Pathway Represses Nanog in Murine Embryonic Stem Cells Takashi Hamazaki, Sarah M. Kehoe, Toru Nakano, Naohiro ... Tyrosine Phosphorylation of Grb2: Role in Prolactin/Epidermal Growth Factor Cross Talk in Mammary Epithelial Cell Growth and ... Activation of the Epidermal Growth Factor (EGF) Receptor Induces Formation of EGF Receptor- and Grb2-Containing Clathrin-Coated ...
Protein (Myc-DYKDDDDK Tag). Species: Human. Source: HEK-293 Cells. Order product ABIN2722222. ... GRB2-Related Adaptor Protein (GRAP) protein (Myc-DYKDDDDK Tag) GRB2-Related Adaptor Protein (GRAP) protein (Myc-DYKDDDDK Tag). ... Protein Name GRB2-Related Adaptor Protein (GRAP) show synonyms for this antigen * 8430435N19Rik ... Protein Type Recombinant Purification tag / Conjugate This GRAP protein is labelled with Myc-DYKDDDDK Tag. Application Antibody ...
This gene encodes a member of the GRB2/Sem5/Drk family and functions as a cytoplasmic signaling protein which contains an SH2 ... This protein also associates with the Ras guanine nucleotide exchange factor SOS1 (son of sevenless homolog 1) through its N- ...
A Rabbit polyclonal antibody against Mouse GRB2 Related Adaptor Protein 2 (GRAP2). This antibody is labeled with HRP. Sequence ... Product GRB2 Related Adaptor Protein 2 (GRAP2) Polyclonal Antibody (Mouse), HRP From Cloud-Clone - ... GRB2 Related Adaptor Protein 2 (GRAP2) Polyclonal Antibody (Mouse), HRP. Supplier Cloud-Clone · Catalog number: 4-PAH967Mu01- ... A Rabbit polyclonal antibody against Mouse GRB2 Related Adaptor Protein 2 (GRAP2). This antibody is labeled with HRP. * ...
Protein Coding), GRB2 Related Adaptor Protein Like, including: function, proteins, disorders, pathways, orthologs, and ... Protein Symbol:. Q8TC17-GRAPL_HUMAN. Recommended name:. GRB2-related adapter protein-like. Protein Accession:. Q8TC17. ... GRAPL (GRB2 Related Adaptor Protein Like) is a Protein Coding gene. Diseases associated with GRAPL include Cantu Syndrome and ... Protein Expression for GRAPL Gene. See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB ...
GRB2-related adaptor protein 2 Chains: A, B Molecule details › Chains: A, B. Length: 100 amino acids. Theoretical weight: 11.82 ... by the adaptor Gads. Cho S, Velikovsky CA, Swaminathan CP, Houtman JC, Samelson LE, Mariuzza RA ... Experimental detection of short regulatory motifs in eukaryotic proteins: tips for good practice as well as for bad. Gibson et ... GRB2-related adaptor protein 2. > SH2 domain superfamily Structure domain: * Occurring in:. *GRB2-related adaptor protein 2. ...
Adaptor Proteins, Signal Transducing * Adaptor Proteins, Vesicular Transport * GRB2 Adaptor Protein * Grb2 protein, mouse ... Analysis of protein-protein interactions involved in the activation of the Shc/Grb-2 pathway by the ErbB-2 kinase Oncogene. ... This network of protein-protein interactions may reflect the ability of the Shc/Grb-2 pathway to act as a molecular switch ... Shc/Grb-2 and Grb-2/ErbB-2 complexes. Tyr 1139 of ErbB-2 bound to the Grb-2 SH2 domain in vitro as well as in intact cells. Tyr ...
... its interaction with the adaptor protein SHC and by the presence of five proline-rich stretches in its non-catalytic carbox … ... The involvement of murine protein tyrosine phosphatase-PEST (MPTP-PEST) in signal transduction pathways is suggested by its ... Wild type Grb2, but not Grb2 proteins corresponding to loss-of-function mutants in the Caenorhabditis elegans sem-5 protein, ... its interaction with the adaptor protein SHC and by the presence of five proline-rich stretches in its non-catalytic carboxyl ...
GRB2-related adapter protein is a protein that in humans is encoded by the GRAP gene. This gene encodes a member of the GRB2/ ... "Entrez Gene: GRAP GRB2-related adaptor protein". Zhang W, Sloan-Lancaster J, Kitchen J, Trible RP, Samelson LE (Jan 1998). "LAT ... "Detection of Grb-2-related adaptor protein gene (GRAP) and peptide molecule in salivary glands of MRL/lpr mice and patients ... Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (May 1996). "Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine ...
Adapter protein GRB2; SH2_SH3 adapter GRB2; Protein Ash \ 10-288-22538F for more molecular products just contact us ... GRB2 ASH] Growth factor receptor-bound protein 2 (Adapter protein GRB2) (Protein Ash) (SH2/SH3 adapter GRB2). [IGF1 IBP1] ... SH3 adapter GRB2; Protein Ash Related products : Growth factor receptor-bound protein 2 - Adapter protein GRB2; SH2_SH3 adapter ... Product name : Growth factor receptor-bound protein 2 - Adapter protein GRB2; SH2_SH3 adapter GRB2; Protein Ash ...
Target GRB2-Binding Adaptor Protein, Transmembrane (GAPT) * GRB2-Binding Adaptor Protein, Transmembrane (GAPT) ... GRB2-binding transmembrane adaptor , growth factor receptor-bound protein 2-binding adapter protein, transmembrane , protein ... anti-GAPT Antikörper (GRB2-Binding Adaptor Protein, Transmembrane) (AA 84-112) Primary Antibody GAPT Reaktivität: Human WB Wirt ... anti-GAPT Antikörper (GRB2-Binding Adaptor Protein, Transmembrane) Primary Antibody GAPT Reaktivität: Human IF (p), IHC (p), WB ...
ID:10006) We have successfully demonstrated that the transmembrane adaptor SIT i is a negative regulator of TCR-mediated ... Trapping Grb2 within immune cells: the role of transmembrane adaptor proteins. DFG FOR 521. Projektleiter:. Simeoni, Luca; Prof ... ERK, Grb2, LAT, LAX, NTAL, TCR-mediated signalling, adaptor protein, knockout mice ... Interestingly, the adaptors NTAL, LAT and LAX might share redundant functions as together they possess 14 Grb2-binding site. ...
Growth factor receptor-bound protein 2. CHICK. 217. GRB2-related adapter protein. BOVIN ... View protein in InterPro. IPR035643, GRB2_C_SH3. IPR035641, GRB2_N_SH3. IPR000980, SH2. IPR036860, SH2_dom_sf. IPR036028, ... View protein in InterPro. IPR035643, GRB2_C_SH3. IPR035641, GRB2_N_SH3. IPR000980, SH2. IPR036860, SH2_dom_sf. IPR036028, ... Protein predictedi ,p>This indicates the type of evidence that supports the existence of the protein. Note that the protein ...
Grb2. Grb2 is one of the best-characterized SH2 adaptor proteins. Grb2 is a 27-kDa molecule with an SH3-SH2-SH3 domain ... SH2 adaptor proteins. SH2 adaptor proteins recognize and bind to tyrosine-phosphorylated proteins by their SH2 domains. They do ... These proteins include adaptors (14-3-3 proteins), transforming proteins (SV40 large T antigen), structural proteins (integrins ... In addition to these adaptor proteins, other SH2 proteins, such as Crk (adaptor), Nck (adaptor), Fyn (tyrosine kinase), and Csk ...
Ab116430 is a full length protein produced in Escherichia coli and has been validated in WB, ELISA, SDS-PAGE, MS. Abcam… ... Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. ... Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active ... Proteins and Peptides. Proteomics tools. Agonists, activators, antagonists and inhibitors. Lysates. Multiplex miRNA assays. By ...
A new function for phospholipase C-gamma1: coupling to the adaptor protein GRB2. ... Differential translocation of protein kinase C isozymes by phorbol esters, EGF, and ANG II in rat liver WB cells. ... Epidermal growth factor and angiotensin II regulation of extracellular signal-regulated protein kinase in rat liver epithelial ... Angiotensin II induces diverse signal transduction pathways via both Gq and Gi proteins in liver epithelial cells. ...
GRB2-related adaptor protein 2, isoform CRA_aImported. ,p>Information which has been imported from another database using ... cDNA, FLJ93267, Homo sapiens GRB2-related adaptor protein 2 (GRAP2), mRNAImported. ,p>Information which has been imported from ... Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. Q6FI14. O75791. B1AH86. B7Z8E3. Homo sapiens ( ... Protein. Similar proteins. Organisms. Length. Cluster ID. Cluster name. Size. Q6FI14. O75791. B1AH86. B7Z8E3. L9KNX9. ...
SHC, Grb2, and SOS are adaptor proteins. Other abbreviations are indicated in the legend to Figure 2. ... MAPK activated protein kinase 2; PLC, phospholipase C; CAMK, calmodulin-dependent protein kinase; PKA, protein kinase A; AC, ... Inhibition of cAMP-response element-binding protein activity decreases protein kinase B/Akt expression in 3T3-L1 adipocytes and ... Acetylation of cAMP-responsive element-binding protein (CREB) by CREB-binding protein enhances CREB-dependent transcription. J ...
Rabbit polyclonal GRB2 antibody. Validated in WB, IHC and tested in Human. Cited in 1 publication(s). Immunogen corresponding ... Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. ... Recombinant Human GRB2 protein (ab85917) can be used as a positive control in WB. Human Brain, Cerebellum, Human Brain, Cortex ... Isoform GRB3-3 acts as a dominant negative protein over GRB2 and by suppressing proliferative signals, may trigger active ...
Protein Coding), Growth Factor Receptor Bound Protein 2, including: function, proteins, disorders, pathways, orthologs, and ... Molecular function for GRB2 Gene. UniProtKB/Swiss-Prot Function: Adapter protein that provides a critical link between cell ... Protein Symbol:. P62993-GRB2_HUMAN. Recommended name:. Growth factor receptor-bound protein 2. Protein Accession:. P62993. ... GeneCards Summary for GRB2 Gene GRB2 (Growth Factor Receptor Bound Protein 2) is a Protein Coding gene. Diseases associated ...
"The oncogenic versions of the Ret and Trk tyrosine kinases bind Shc and Grb2 adaptor proteins". Oncogene. 9 (6): 1661-8. PMID ... protein kinase activity. • kinase activity. • protein binding. • protein tyrosine kinase activity. • ATP binding. • Ras guanyl- ... "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): ... membrane protein proteolysis. • phosphorylation. • transmembrane receptor protein tyrosine kinase signaling pathway. • positive ...
"Networks of interaction of p120cbl and p130cas with Crk and Grb2 adaptor proteins". Oncogene. 12 (12): 2491-8. PMID 8700507. ... of adaptor proteins which is characterized by the presence of multiple conserved motifs for protein-protein interactions, and ... p130Cas/BCAR1 belongs to the Cas family of adaptor proteins and can act as a docking protein for several signalling partners. ... Brinkman A, van der Flier S, Kok EM, Dorssers LC (Feb 2000). "BCAR1, a human homologue of the adapter protein p130Cas, and ...
... proteins. One of the adaptor proteins, GRB2 recruits SOS to the membrane. SOS activates GDP/GTP exchange which recruits RAF to ... The EGFR signaling cascade has an adaptor protein complex containing the growth factor receptor bound protein 2 (Grb2) and the ... R-SMAD proteins, or SMAD4. Overexpression of inhibitory SMAD6 or SMAD7 proteins, blocking phosphorylation of R-SMAD proteins, ... Multiple proteins contribute to the recruitment of R-SMAD proteins to TGFBR1s and enhance SMAD activation, including SARA, ...
Adaptor proteins Grb2 and Crk couple Pyk2 with activation of specific mitogen-activated protein kinase cascades. ... G protein-coupled receptor-mediated mitogen-activated protein kinase activation through cooperation of Galpha(q) and Galpha(i) ... Phosphorylation and regulation of a G protein-coupled receptor by protein kinase CK2. ... Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in ...
Possible facilitation by the formation of a ternary complex with the Grb2 adaptor protein. J Biol Chem. 2000;275(6):4283-4289. ... we observed increases in Mer and Tyro3 surface protein (Supplemental Figure 8). The RNA/protein discrepancy may be attributable ... We hypothesize that Grb2, which has been demonstrated to interact with both Mer (23) and PTP1b (51), is a likely intermediary. ... Protein tyrosine phosphatase 1B is a key regulator of IFNAR1 endocytosis and a target for antiviral therapies. Proc Natl Acad ...
For the v-Abl protein, the Shc adapter molecule is one such substrate (31, 35). Shc can complex with Grb2 and the G-protein ... Activation of c-Myc expression requires an active Ras protein (52), and the decreased association of Shc and Grb2 at 39.5°C is ... 1994) The GRB2/Sem-5 adaptor protein. FEBS Lett. 338:113-117. ... Protein was quantitated using a bicinchoninic acid protein ... 1997) Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking protein, Dok. Cell 88:205-211. ...
... coupling to the adaptor protein GRB2". Archives of Biochemistry and Biophysics. 345 (1): 103-10. doi:10.1006/abbi.1997.0245. ... Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (February 1996). "A Grb2-associated docking protein in EGF- and ... Oneyama C, Nakano H, Sharma SV (March 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction ... "Brain-derived neurotrophic factor promotes interaction of the Nck2 adaptor protein with the TrkB tyrosine kinase receptor". ...
GRB2-related adapter protein 2 Enzyme Information. UniProtKB Entries (2). O89100. GRAP2_MOUSE ... CATH: Protein Structure Classification Database by I. Sillitoe, N. Dawson, T. Lewis, D. Lee, J. Lees, C. Orengo is licensed ...
The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and ... Background: Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases ... Background: Lysosome-associated membrane protein 1 and 2 (LAMP1 and LAMP2) are two abundant lysosomal membrane proteins (1,2). ... Ubiquitin can be covalently linked to many cellular proteins by the ubiquitination process, which targets proteins for ...
The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and ... The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and ... These sites serve as consensus binding sites for signal transducing proteins, including Src family members, Grb2, and the p85 ... These sites serve as consensus binding sites for signal transducing proteins, including Src family members, Grb2, and the p85 ...
  • Together, these results describe a novel SH3 domain-dependent recruitment of a protein tyrosine phosphatase to an activated receptor tyrosine kinase and establish a potential role for MPTP-PEST in signalling pathways at the molecular level. (nih.gov)
  • This results in activation of the receptor kinase and tyrosine phosphorylation of a family of insulin receptor substrate (IRS) proteins. (jci.org)
  • PI3-kinase is critical for metabolic actions of insulin, such as glucose transport, glycogen synthesis, and protein synthesis, whereas Grb-2/SOS complex, which activates the MAP kinase cascade, is critical in mitogenic response. (jci.org)
  • Gene Ontology (GO) annotations related to this gene include protein kinase binding . (genecards.org)
  • The first kinase identified as being responsible for the phosphorylation of serine 133 is a cAMP-dependent protein kinase (protein kinase A [PKA]), which is activated by an increase in the intracellular cAMP level. (ahajournals.org)
  • This acts as a protein-interaction motif, similar to those found in other adhesion-related proteins such as focal adhesion kinase (FAK) and vinculin. (wikipedia.org)
  • Each protein is divided into three domains: an N-terminal extracellular domain with four cadherin -like repeats and a cysteine -rich region, a hydrophobic transmembrane domain and a cytoplasmic tyrosine kinase domain, which is split by an insertion of 27 amino acids . (wikipedia.org)
  • [5] The structure is that of a dimer formed between two protein molecules each spanning amino acids 703-1012 of the RET molecule, covering RETs intracellular tyrosine kinase domain. (wikipedia.org)
  • In this review, we will focus on the mitogen-activated protein kinase (MAPK) cascades downstream of the epidermal growth factor receptor (EGFR), Notch, PI3K/AKT pathway, transforming growth factor-β (TGF-β), and Wnt signaling pathways. (springer.com)
  • EGFR is a transmembrane protein belonging to the ErbB family of receptors, which functions as a receptor tyrosine kinase (RTK). (springer.com)
  • Also, this protein has been shown to be a major substrate for heparin-binding growth factor 1 (acidic fibroblast growth factor)-activated tyrosine kinase. (wikipedia.org)
  • Overcoming hypoxia-induced tumor radioresistance in non-small cell lung cancer by targeting DNA-dependent protein kinase in combination with carbon ion irradiation. (nih.gov)
  • Abelson murine leukemia virus (Ab-MLV) encodes the v-Abl protein tyrosine kinase and induces transformation of immortalized fibroblast lines and pre-B cells. (asm.org)
  • Temperature-sensitive mutations affecting the kinase domain of the protein have demonstrated that the kinase activity is absolutely required for transformation. (asm.org)
  • Expression of the protein tyrosine kinase encoded by the v- abl oncogene of Abelson murine leukemia virus (Ab-MLV) induces transformation of pre-B cells and immortalized fibroblast lines in vitro and causes pre-B-cell lymphoma in mice ( 37 ). (asm.org)
  • Although the tyrosine kinase activity of the v-Abl protein is absolutely required for transformation, the SH2 domain, a region involved in phosphotyrosine-dependent interactions ( 11 , 48 ), also plays an important role in the process. (asm.org)
  • The resultant stimulation of Ras activates a mitogen-activated protein kinase cascade, leading to cell growth and differentiation. (sciencemag.org)
  • GRAP2 is an adaptor-like protein has a part in leukocyte-specific protein-tyrosine kinase signaling. (prospecbio.com)
  • Inhibition of Protein Kinase C suppresses megakaryocytic differentiation and stimulates erythroid differentiation in HEL cells. (springer.com)
  • This member is an adaptor-like protein involved in leukocyte-specific protein-tyrosine kinase signaling. (abnova.com)
  • Inhibition of Bcr-Abl tyrosine kinase activity or signaling proteins activated by Bcr-Abl in CML cells blocks proliferation and causes apoptotic cell death. (aacrjournals.org)
  • This reciprocal translocation fuses the ABL locus on chromosome 9 with the BCR locus on chromosome 22, resulting in expression of the constitutively active protein tyrosine kinase Bcr-Abl. (aacrjournals.org)
  • Epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase belonging to the HER/ErbB protein family, and expressed by epithelial and endothelial cells. (fluidigm.com)
  • The Caenorhabditis elegans mpk-1 gene encodes a MAP kinase protein that plays an important role in Ras-mediated induction of vulval cell fates. (genetics.org)
  • In addition to nuclear targets, some MAP kinase substrates are located in the cytoplasm, e.g. , the guanine nucleotide exchange factor SOS and the protein kinase pp90Rsk (reviewed in F errell 1996 ). (genetics.org)
  • The phosphatidylinositol (PI) 3-kinase (PI3K) signaling pathway is a normal signal transduction cascade that exists in all types of cells and is physiologically involved in cell proliferation, survival, protein synthesis, metabolism, differentiation, and motility. (hindawi.com)
  • Pleckstrin homology domain leucine-rich repeat protein phosphatase functions as a "brake" for Akt and protein kinase C signaling, which has been extensively reviewed [ 16 ]. (hindawi.com)
  • This recruits the Grb2 adaptor protein and effector proteins such as phosphatidylinositol 3-kinase (PI3K) or phospholipase-Cγ (PLC-γ) to initiate downstream signaling pathways that contribute to oncogenesis and cancer cell proliferation ( 4 ). (sciencemag.org)
  • For instance, besides the two distal ITIMs in the cytoplasmic tail of CD22 that recruit the protein tyrosine phosphatase (PTP), SHP-1, another motif, Y828 (or mouse Y807), when tyrosine phosphorylated, binds Grb2 and Shc and, forms a complex with SHIP and activation of a MAP kinase pathway that can regulate cell survival and proliferation ( 5 - 7 ). (frontiersin.org)
  • On phosphorylation of Y221 by Abelson (Abl) kinase, the Crk-II adapter protein undergoes an intramolecular reorganization initiated by the binding of its own Src homology 2 (SH2) domain to the pY221 site. (pnas.org)
  • An interesting example in this context is provided by the protein interactions observed between the Abelson (Abl) tyrosine kinase and the adapter protein Crk-II. (pnas.org)
  • Abl kinase interacts with the Crk adapter protein in distinct ways depending on the isoform and the phosphorylation state of Y221 in Crk. (pnas.org)
  • The PDGFs bind to the protein tyrosine kinase receptors PDGF receptor-α and -β. (wikidoc.org)
  • Ras mediates its effect on cell proliferation mainly by activation of its effector Raf to initiate the mitogen-activated protein kinase (MAPK/extracellular signal regulated kinase [ERK]) cascade. (ahajournals.org)
  • Chronic Myelogenous Leukemia (CML) It's effect on G-Protein-Linked Receptors It is a membrane receptor that works with the help of a G protein Receptor Tyrosine Kinase A receptor tyrosine kinase can trigger more than one signal transduction pathway at once. (prezi.com)
  • A protein kinase is an enzyme that phosphorylates a molecule Ion Channel Receptors It is a type of membrane receptor in which a region acts as a gate when the receptor changes shape. (prezi.com)
  • The immediate effect of the cAMP is the activation of a serine/threonine kinase called 'protein kinase A.' It is more widely used as a second messenger than cAMP. (prezi.com)
  • DAG activates protein kinase C pathway. (wikipathways.org)
  • Habib AA, Chatterjee S, Park SK, Ratan RR, Lefebvre S, Vartanian T. The epidermal growth factor receptor engages receptor interacting protein and nuclear factor-kappa B (NF-kappa B)-inducing kinase to activate NF-kappa B. Identification of a novel receptor-tyrosine kinase signalosome. (proteopedia.org)
  • In particular, the phosphoinositide 3-kinase (PI3K)/AKT pathway can be effectively blocked by mTOR inhibitors, and several compounds can hit the RAS pathway and the resulting mitogen-activated protein (MAP) extracellular signal-regulated kinase (ERK)1/2 (MEK) and MAP kinase activation. (aacrjournals.org)
  • Examples include the perturbation of the Ras-mitogen-activated protein kinase (MAPK) leading to increased proliferation, the Janus-activated kinase (JAK)-STAT pathway leading to impaired transcriptional activity, and the phosphoinositide 3-kinase (PI3K)/AKT pathway resulting in increased apoptosis ( 8 ). (aacrjournals.org)
  • As a consequence, the GRB2/GAB2/SOS complex causes constitutive activation of the RAS downstream pathway, thereby activating mitogen-activated protein (MAP) extracellular signal-regulated kinase (ERK)1/2 (MEK) and MAP kinase proteins and resulting in abnormal cell proliferation. (aacrjournals.org)
  • CD28 has been reported to bind to phosphatidylinositol 3-kinase (PI3-K), adaptors Grb-2/GADS, and the phosphatase PP2A ( 6 - 11 ), while CTLA-4 binds to PI3-K and phosphatases PP2A and SHP-2 ( 11 - 14 ). (rupress.org)
  • The most recently described member of the pTRAP family is SLP adaptor and C-terminal Src kinase (CSK)-interacting membrane protein (SCIMP), which has been reported to associate with Src family kinases (SFKs) and to regulate MHC class II signalling in B cells 18 and Dectin-1 signalling in dendritic cells 19 . (nature.com)
  • CIN85 was independently identified as a Cbl-interacting protein of 85 kDa ( 6 ), Ruk (regulator of ubiquitous kinase) ( 7 ), SETA (SH3 domain-containing gene expressed in tumorigenic astrocytes) ( 8 ), and SH3KBP1 (SH3 domain-containing kinase binding protein 1) ( 9 ). (diabetesjournals.org)
  • Rasl and a putative guanine nucleotide exchange factor perform crucial steps in signaling by the sevenless protein tyrosine kinase. (springer.com)
  • Basler K, Hafen E. Control of photoreceptor cell fate by the sevenless protein requires a functional tyrosine kinase domain. (springer.com)
  • The kinase TAK1, a mitogen-activated protein kinase kinase kinase (MAP3K), has been widely accepted as a key kinase activating NF-κB and MAPKs in tumor necrosis factor alpha (TNF-α) signaling. (pubmedcentralcanada.ca)
  • In turn, Shc binds Grb2 and Sos, which result in the rapid activation of mitogen-activated protein kinase. (aacrjournals.org)
  • The mechanistic pathways involved in adaptive hypersensitivity suggest that inhibitors of the mitogen-activated protein kinase and phosphatidylinositol-3-OH kinase pathways might prevent the development of adaptive hypersensitivity and allow more prolonged efficacy of endocrine therapies. (aacrjournals.org)
  • The RASopathies comprise a recognizable pattern of malformation syndromes that are caused by germ line mutations in genes that encode components of the RAS/mitogen-activated protein kinase (MAPK) pathway. (stanford.edu)
  • Abstract -The aim of this study was to elucidate the upstream signaling mechanism that mediates the fluid shear stress activation of mitogen-activated protein kinases (MAPKs), including c-Jun NH 2 -terminal kinase (JNK) and extracellular signal-regulated kinases (ERKs), in vascular endothelial cells (ECs). (ahajournals.org)
  • The protein encoded by this gene is the principal activator of phosphatidylinositol-3 kinase in response to activation of the high affinity IgE receptor. (thermofisher.com)
  • ribosomal protein S6 kinase, 70kDa, polyp. (broadinstitute.org)
  • In the present study an attempt was made to further elucidate the molecular mechanisms whereby protein kinase C (PKC) modulates the beta-cell stimulus-secretion coupling. (diva-portal.org)
  • Protein kinase activity is rapidly up-regulated by ethylene, the effect is inhibited by 1-methylcyclopropene, and the activation is bimodal. (plantphysiol.org)
  • Implicit in the presence of a putative MAPKKK in the transduction sequence is that protein phosphorylation via a mitogen-activated protein kinase (MAPK) cascade(s) is involved in mediating responses to ethylene. (plantphysiol.org)
  • Equally, there is evidence that ethylene affects protein kinase activity. (plantphysiol.org)
  • Grb2-related adaptor protein-2 (GRAP2, GADS, 330 aa) is another of the Grb2/Sem5/Drk family and reportedly involved in leucocyte-specific protein tyrosine kinase signalling. (oup.com)
  • Egf (EGF) binds to the Egf receptor (EgfR) and stimulates its protein tyrosine kinase activity to cause autophosphorylation, thus activating EgfR. (coursehero.com)
  • The EgfR complex activates a Ras family GTPase Activated Ras activates Raf1, a member of the RAF serine/threonine protein kinase family. (coursehero.com)
  • from Wikipedia Egf stimulation of the Mitogen Activated Protein Kinase (MAPK) pathway. (coursehero.com)
  • Antigen binding to the T cell receptor (TCR) can also lead to Ras signaling through activation of phospholipase C (PLC) and protein kinase C (PKC). (biolegend.com)
  • 1995 ). Interaction of focal adhesion kinase with cytoskeletal protein talin. (biologists.org)
  • Proline-rich sequences have been identified as binding sites for Src homology 3 (SH3) domains found in proteins associated with signal transduction events. (nih.gov)
  • Some of the best-characterized protein interaction domains involved in insulin signaling are the PH (pleckstrin homology), PTB (phosphotyrosine binding), SH2, and SH3 domains ( 1 ) (Table 1 ). (jci.org)
  • These Cas proteins have a high structural homology, characterized by the presence of multiple protein interaction domains and phosphorylation motifs through which Cas family members can recruit effector proteins. (wikipedia.org)
  • B cell linker protein (BLNK) and Src homology 2 domain-containing leukocyte protein of 76 kD (SLP-76) are adaptor proteins required for B cell receptor (BCR) and T cell receptor function, respectively. (nih.gov)
  • Src homology (SH) domains, including SH2 and SH3 domains, are protein modules found in many otherwise functionally distinct molecules ( 25 ). (asm.org)
  • Recent studies provided evidence of distinct functions of the four main phosphatases-phosphatase and tensin homologue deleted on chromosome 10 (PTEN), Src homology 2-containing inositol 5′-phosphatase (SHIP), inositol polyphosphate 4-phosphatase type II (INPP4B), and protein phosphatase 2A (PP2A)-in different tissues with respect to regulation of cancer development. (hindawi.com)
  • PP2C (pleckstrin homology domain leucine-rich repeat protein phosphatase) belongs to a novel PP2C-type phosphatase family, the PPM subfamily. (hindawi.com)
  • The Src homology 2 (SH2) domain is the archetypal protein-interaction module. (sciencemag.org)
  • Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein with three Src homology (SH) domains in the order SH3-SH2-SH3. (rcsb.org)
  • In particular, the Src homology 2 (SH2) and Src homology 3 (SH3) domains of cytoplasmic tyrosine kinases and associated adapter proteins demonstrate a wide variety of regulatory mechanisms involving both intramolecular and intermolecular interactions with target peptide regions ( 3 , 4 ). (pnas.org)
  • The proteins recruited to active EGFR include many Src homology 2 (SH2) and phosphotyrosine binding (PTB) domain containing proteins which binds to the tyrosine phosphorylated residues in EGFR, enzymes which act on EGFR and also various EGFR substrates. (wikipathways.org)
  • Such motifs in other proteins are known to mediate protein-protein interactions such as with Src homology (SH)3 domains. (pnas.org)
  • These proteins contain pleckstrin homology (PH) domain, and bind SHP2 tyrosine phosphatase and GRB2 adapter protein. (thermofisher.com)
  • has shown that, in tomato ( Lycopersicon esculentum ) fruit, the transcription of a gene, which showed high homology to a monomeric G-protein from pea, is rapidly but transiently up-regulated by ethylene. (plantphysiol.org)
  • Some other putative IGF-binding proteins with less sequence homology have been found, but they have not been well studied [ 3 ]. (biomedcentral.com)
  • Grb2-associated binder-1 (gab-1, 694 aa) binds to Grb-2 and has homology with IRS-1 (insulin receptor substrate-1). (oup.com)
  • The phosphorylated insulin receptor binds and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins. (jci.org)
  • The protein encoded by this gene binds the epidermal growth factor receptor and contains one SH2 domain and two SH3 domains. (genecards.org)
  • Its two SH3 domains direct complex formation with proline-rich regions of other proteins, and its SH2 domain binds tyrosine phosphorylated sequences. (genecards.org)
  • and the SH3 domain binds to proline-rich sequences on the target protein. (wikipedia.org)
  • Grb2 binds to two separate pY-X-N-V motifs in the epidermal growth factor receptor (EGFR) via its SH2 domain and associates through its two SH3 domains to the PPPVPPRRR motifs in Sos, a guanine nucleotide exchange factor for Ras. (asm.org)
  • The Grb2 adapter protein binds activated EGFR at phospho-Tyr1068. (fluidigm.com)
  • Cells communicate by signals sent from other cells that they then traduce to trigger a specific cellular response Through Signal Transduction Pathway Stages Types of pathways Reception Transduction Response Reception is the detection of the signal molecule by the target cell, which senses it when it binds to the receptor protein at the cell's surface. (prezi.com)
  • When the signal molecule binds to the receptor protein, the gate opens allowing or blocking a flow of ions into the cell. (prezi.com)
  • One of the adapter proteins, GRB2, binds to the phosphotyrosine residue at 1068 and recruits SOS to the membrane. (wikipathways.org)
  • The aminoterminal BCR -encoded sequences of BCR-ABL contain a tyrosine-phosphorylated site that binds the SH2 domain of the adaptor protein GRB2 ( 6 ). (aacrjournals.org)
  • Estradiol binds to cell membrane-associated ERs, physically associates with the adaptor protein Shc, and induces its phosphorylation. (aacrjournals.org)
  • Like other growth factors, insulin uses phosphorylation and the resultant protein-protein interactions as essential tools to transmit and compartmentalize its signal. (jci.org)
  • 5 On phosphorylation at serine 133, the CREB binding protein (CBP) is recruited to CREB. (ahajournals.org)
  • Due to the capacity of p130Cas/BCAR1, as an adaptor protein, to interact with multiple partners and to be regulated by phosphorylation and dephosphorylation, its expression and phosphorylation can lead to a wide range of functional consequences. (wikipedia.org)
  • p130Cas/BCAR1 tyrosine phosphorylation can result from a diverse range of extracellular stimuli, including growth factors, integrin activation, vasoactive hormones and peptides ligands for G-protein coupled receptors. (wikipedia.org)
  • Temperature-dependent transformation was accompanied by decreased phosphorylation of Shc, a protein that interacts with the v-Abl SH2 and links the protein to Ras, and decreased induction of c-Myc expression. (asm.org)
  • Growth factor stimulation leads to the activation of receptor tyrosine kinases and to the phosphorylation of the receptor tail and the stimulation of phosphorylation of related adaptor proteins (not shown). (sciencemag.org)
  • Thus, SH2 and SH3 domains act as a second messenger connecting protein tyrosine phosphorylation to a variety of intracellular signaling networks. (asm.org)
  • SKI-606 inhibits phosphorylation of cellular proteins, including STAT5, at concentrations that inhibit proliferation in CML cells. (aacrjournals.org)
  • Most SH2 domain-containing proteins are recruited to sites of tyrosine phosphorylation to aid in the construction of molecular machines ( 3 ). (sciencemag.org)
  • 8 ) reported that BCR ligation leads to rapid tyrosine phosphorylation of both the classic ITIMs and the Grb2 recruitment motif, while CD40 ligation only induces tyrosine phosphorylation of the ITIM domains. (frontiersin.org)
  • Galisteo ML, Dikic I, Batzer AG, Langdon WY, Schlessinger J. Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association with epidermal growth factor (EGF) receptor upon EGF stimulation. (proteopedia.org)
  • It is now evident that the phosphorylation of BCR Tyr177 is essential for BCR-ABL-mediated leukemogenesis ( 9 ), and its mutation largely abolishes GRB2 binding and diminishes BCR-ABL-induced Ras activation ( 7 ). (aacrjournals.org)
  • Phosphorylation of Y 682 has profound effects on APP protein-protein interactions. (jneurosci.org)
  • Phosphorylation of EGFR at Y1086 specifically allows binding of the adaptor protein GRB2, leading to activation of the MAPK pathway. (thermofisher.com)
  • GTP-bound Ras activates Raf to trigger a phosphorylation cascade involving mitogen-activated protein kinases (MEKs). (biolegend.com)
  • In vitro binding assays indicate that four of these proline-rich sequences constitute specific binding sites for both SH3 domains of the adaptor molecule Grb2. (nih.gov)
  • One protein molecule, molecule A is shown in yellow and the other, molecule B in grey. (wikipedia.org)
  • For the v-Abl protein, the Shc adapter molecule is one such substrate ( 31 , 35 ). (asm.org)
  • Thus, GRB2 mediates signal transduction from growth factor receptors to Ras and is thought to be a key molecule in signal transduction. (rcsb.org)
  • The TLR adaptor molecule, Toll/IL-1R domain-containing adaptor inducing IFN (TRIF), facilitates TLR3 and TLR4 signaling and concomitant activation of the transcription factors, NF-κB and IFN regulatory factor 3, leading to proinflammatory cytokine production. (jimmunol.org)
  • The binding of the signal molecule changes the shape of the receptor protein, initiating the transduction process. (prezi.com)
  • Previous studies have shown that shear stress induces several genes that encode proteins implicated in atherosclerosis and other vascular diseases, including MCP-1, intercellular adhesion molecule-1, heparin-binding EGF-like growth factor, PDGF, nitric oxide synthase, and c- fos proto-oncogene. (ahajournals.org)
  • GRAP2 belongs to the GRB2/Sem5/Drk family. (prospecbio.com)
  • The GRAP2 protein solution (0.5mg/ml) is formulated in 20 mM Tris-HCl buffer (pH8.0), 0.2M NaCl, 5mM DTT, 1mM EDTA and 30% glycerol. (prospecbio.com)
  • Human GRAP2 partial ORF ( AAH25692, 226 a.a. - 315 a.a.) recombinant protein with GST-tag at N-terminal. (abnova.com)
  • Orthologous to human GRAP2 (GRB2 related adaptor protein 2). (zfin.org)
  • Experiments in EGF receptor expressing cells show that the interaction between MPTP-PEST and Grb2 results in the binding of this complex to activated EGF receptors. (nih.gov)
  • Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. (abcam.com)
  • The co-receptors themselves are classified as members of the GDNF receptor-α (GFRα) protein family. (wikipedia.org)
  • 3 Activation of these receptors results in stimulation of signal-transduction pathways culminating in release of water, electrolytes, and proteins across the apical membranes and into the glandular excretory duct and onto the ocular surface. (arvojournals.org)
  • In hepatoma HTC4 cells ( 15 ), exogenous S1P exerts its antiapoptotic activity, which is mediated by G protein-coupled receptors encoded by the endothelial differentiation gene (Edg) 3 and 5. (jimmunol.org)
  • There are ≥2 transmembrane G protein-coupled receptors (GPCRs) known to mediate Ang II function, namely, the type 1 and type 2 (AT 1 and AT 2 ) receptors. (ahajournals.org)
  • Grb2 encodes an adaptor protein involved in signal transduction from cell surface growth factor receptors and mediates Ras, Raf, and ERK1/2 activation. (jax.org)
  • I trained as a postdoctoral fellow from 1986 to 1989 at the University of California, San Francisco, and at Genentech, studying G protein-coupled receptors. (gene.com)
  • However, this approach does not necessarily recapitulate the physiological process of intercellular communication, in part because protein ligands for some transmembrane receptors may themselves be attached to the surface of cells. (sciencemag.org)
  • The Toll-like receptors (TLRs), single-pass transmembrane proteins at the cell surface and in endolysosomal compartments, are the most extensively studied of the pattern recognition receptors. (nature.com)
  • Several G-protein coupled receptors, such as the β1-adrenergic receptor (β1-AR), contain polyproline motifs within their intracellular domains. (pnas.org)
  • β-adrenergic receptors (βARs) belong to a large family of G-protein-coupled receptors that contain seven transmembrane domains connected by three extracellular loops, three intracellular loops, and a carboxyl terminal tail. (pnas.org)
  • More intriguingly, this sequence feature also can be found in other G-protein coupled receptors (GPCRs), including β3-AR, α2A-AR, and dopamine D4 receptors ( 14 ). (pnas.org)
  • In the case of dopamine D4 receptors, these proline-rich motifs were demonstrated, in vitro , to serve as potential ligands for several SH3 domain-containing proteins, such as Nck and Grb2 ( 14 ). (pnas.org)
  • This complex consists of trimerized receptors, the death domain-containing adaptor protein FADD (Fas-associated death domain protein), and caspase-8. (pubmedcentralcanada.ca)
  • They act as adapters for transmitting various signals in response to stimuli through cytokine and growth factor receptors, and T- and B-cell antigen receptors. (thermofisher.com)
  • Binding of IGFBP proteins with IGF has been shown to either positively or negatively regulate the binding of IGFs to their receptors [ 1 ], thus directly affecting the IGF signaling pathways. (biomedcentral.com)
  • An adaptor protein (growth factor receptor bound protein 2, 217 aa), the mammalian homologue of Caenorhabditis elegans Sem-5 and Drosophila Drk that links the cytoplasmic domain of growth factor receptors to downstream elements of the signalling pathway through its SH2 and SH3 domains. (oup.com)
  • Epidermal growth factor receptor (EGFR, erbB1) activation and translocation of the Shc adaptor protein to activated receptors were analyzed at the subcellular level by dual-label immunofluorescence and confocal laser scanning microscopy in conjunction with a new microsphere-based protocol. (biologists.org)
  • These substrates are commonly referred to as docking proteins, since several other intracellular proteins bind to the phosphorylated substrates, thereby transmitting the signal downstream. (jci.org)
  • Activation of Ras stimulates multiple downstream effector proteins, including c-Myc ( 21-23 ), another protein that is critical for Abl-mediated transformation ( 38 ). (asm.org)
  • Moreover, we demonstrate that addition of both linker for activation of T cells (LAT) and Grb2-related adaptor downstream of Shc (Gads) to SLP-76 allow SLP-76 to be recruited into GEMs, whereby the BCR function is reconstituted. (nih.gov)
  • Similar to Grb2, Nck is widely expressed in various types of cells and acts as an adapter by linking receptor tyrosine kinases to downstream signaling networks. (asm.org)
  • Activation of RTK through diverse mechanisms, including gene mutation, gene amplification, or overproduction of activating growth factor ligands, leads to assembly of protein complexes on RTK that facilitate downstream signal transduction. (aacrjournals.org)
  • These noncatalytic organizing proteins contain a domain that selectively recognizes the activated receptor (an SH2 domain in the case of receptor tyrosine kinases), linked to domains such as SH3, that engage specific downstream targets, typically by binding to proline-rich sequences. (sciencemag.org)
  • Multiple downstream effectors of small G proteins, some of them being protein kinases, have been identified. (ahajournals.org)
  • A targeting vector was designed to insert a loxP site followed by a frt -flanked neomycin resistance (neo) cassette upstream of exon 2, and a second loxP site downstream of exon 2 of the growth factor receptor bound protein 2 ( Grb2 ) gene. (jax.org)
  • The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades. (proteopedia.org)
  • Multiple tyrosine residues of the EGFR intracellular domain are autophosphorylated upon dimerization with ligands such as EGF and, thereafter, recruit a variety of downstream substrates, including Grb2, Shc, and phospholipase C-γ, which trigger signaling waves to mitogen-activated protein kinases (MAPKs) and Akt ( 22 , 23 ). (pubmedcentralcanada.ca)
  • In summary, our studies have demonstrated that transmembrane adaptor molecules represent critical regulators in lymphocyte biology and that redundancy could be a general feature among the adaptors. (forschung-sachsen-anhalt.de)
  • Hence, these data suggest a functional overlap between BLNK and SLP-76, while emphasizing the difference in requirement for additional adaptor molecules in their targeting to GEMs. (nih.gov)
  • Signaling proteins typically have a modular organization, being composed of domains with binding or catalytic functions, interspersed with regions that serve as docking or substrate sites for other molecules. (sciencemag.org)
  • The signal transduction molecules are either equipped with different enzymatic activities, or they are adaptor molecules, which in some but not all cases are found in complexes with subunits that carry a catalytic activity. (wikidoc.org)
  • In this regard, Ras and Rho G proteins are the most investigated molecules in the cardiovascular system. (ahajournals.org)
  • The proteins along the way are usually called 'relay molecules. (prezi.com)
  • This study aims to examine whether the There are several signaling molecules which expression of Grb2 mRNA patients correlated with are overexpressed in human breast cancer, such as incidence of HCMV infection in carcinoma tissues of growth factor receptor-bound 2 (Grb2). (who.int)
  • The latter results from the interaction of BCR-ABL with other cytoplasmic proteins, which function as adaptor molecules, thus creating multiprotein signaling complexes. (aacrjournals.org)
  • The molecules discussed include Src family kinases, Syk, Grb2 adaptor protein, and Tec family kinases Bmx and Btk. (lu.se)
  • Signaling PATHWAYS Signaling pathways involve the modification and/or assembly of proteins and other molecules within cellular compartments into complexes that coordinate and regulate the flow of information. (coursehero.com)
  • Involvement of LAT, Gads, and Grb2 in compartmentation of SLP-76 to the plasma membrane. (nih.gov)
  • The Gads function was able to be replaced by overexpression of Grb2. (nih.gov)
  • The YMNM motif beginning at tyrosine 170 in particular is critical for the recruitment of SH2 -domain containing proteins, especially PI3K , [1] Grb2 [2] and Gads . (wikidoc.org)
  • The N172 residue (as part of the YMNM) is important for the binding of Grb2 and Gads and seems to be able to induce IL-2 mRNA stability but not NF-κB translocation. (wikidoc.org)
  • However, mutation of the final amino acid of the motif, M173, which is unable to bind PI3K but is able to bind Grb2 and Gads, gives little NF-κB or IL-2, suggesting that those Grb2 and Gads are unable to compensate for the loss of PI3K. (wikidoc.org)
  • The involvement of murine protein tyrosine phosphatase-PEST (MPTP-PEST) in signal transduction pathways is suggested by its ability to dephosphorylate phosphotyrosine residues, its interaction with the adaptor protein SHC and by the presence of five proline-rich stretches in its non-catalytic carboxyl terminus. (nih.gov)
  • This mutant encodes a v-Abl protein in which the βB5 arginine at the base of the phosphotyrosine-binding pocket has been replaced by a lysine. (asm.org)
  • Residues within the SH2 domain that contact residues C terminal to the phosphotyrosine on the target protein are one way in which specificity of substrate interaction may be controlled ( 26 , 43 ). (asm.org)
  • SH3-associated proteins often get translocated to the proximity of phosphotyrosine proteins ( 32 ). (asm.org)
  • It links phosphotyrosine-containing motifs (recognized by the SH2 domain) to SH3-binding proteins such as DOCK180 and C3G, which in turn regulate small GTPases involved in cell adhesion and movement ( 14 ). (pnas.org)
  • This increases the number of the phosphotyrosine residues on BCR-ABL and, as a consequence, the binding sites for the SH2 domains of other proteins ( 6, 7 ). (aacrjournals.org)
  • We further demonstrate that this kinetic proofreading is modulated by the LAT (linker for activation of T cells)-Grb2-SOS phosphotyrosine-driven phase transition at the membrane. (stanford.edu)
  • Protein kinases and transcription factors transmit the signals from the external stimuli to the genome, resulting in the modification of gene expression profile of the cells to accommodate to the environmental changes. (ahajournals.org)
  • Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases. (nih.gov)
  • The fact that RTKs and the terminal mitogen-activated protein kinases (MAPKs) can be inducibly recruited to chromatin presents the possibility that canonical insulin signaling pathways are recapitulated along gene loci. (diabetesjournals.org)
  • The SH3-SH3-SH3-SH2 adapter Nck represents a two-gene family that includes Nckα (Nck) and Nckβ (Grb4/Nck2), and it links receptor tyrosine kinases to intracellular signaling networks. (asm.org)
  • EGFR induces the JNK pathway through the activation of G proteins such as RAC and CDC42 which recruits JNK kinases as well as regulate the actin polymerization. (wikipathways.org)
  • Rafts are enriched with GPI-linked proteins, palmitoylated transmembrane adaptors such as LAT (linker for activation of T cells), and myristoylated kinases such as p56 lck and p59 fyn ( 19 - 22 ). (rupress.org)
  • In addition to kinases, rafts are enriched with other signaling proteins. (rupress.org)
  • Members of the transmembrane adaptor protein (TRAP) family scaffold signalling proteins and kinases to support receptor-mediated signalling in other immune cells 11 . (nature.com)
  • The identification of the particular ''PxxPR'' proline motif recognized by CIN85's SH3 domains has led to the discovery of numerous CIN85-interacting proteins, many of which are involved in the formation and trafficking of endocytic vesicles, an essential mechanism for the downmodulation of receptor tyrosine kinases (RTKs), as well as regulation of cell cytoskeleton and phospholipid metabolism ( 10 , 11 ). (diabetesjournals.org)
  • Furthermore, these regions are also critical for binding of βAR regulatory proteins, primarily the G protein-coupled receptor kinases (GRKs) and the β-arrestins ( 9 , 10 ). (pnas.org)
  • It is demonstrated that, in etiolated pea ( Pisum sativum ) epicotyls, ethylene affects the activation of both monomeric GTP-binding proteins (monomeric G-proteins) and protein kinases. (plantphysiol.org)
  • EGFR belongs to the HER/ERbB family of proteins that includes three other receptor tyrosine kinases, ERbB2, ERbB3, ERbB4. (thermofisher.com)
  • Through our participation in the modeling project, it came to our attention that also the function of the cytoplasmic adaptor Grb2 in antigen receptor-mediated signaling is not clearly understood. (forschung-sachsen-anhalt.de)
  • On the basis of these findings, we propose (i) the characterization of Grb2 function in antigen receptor (in particular TCR) signalling and (ii) the investigation of the functional redundancy of Grb2-binding NTAL, LAT and LAX in immune cells. (forschung-sachsen-anhalt.de)
  • Here, we show that expression of SLP-76 cannot reconstitute BCR function in Zap-70(+)BLNK(-) B cells.This could be attributable to inability of SLP-76 to be recruited into glycolipid-enriched microdomains (GEMs) after antigen receptor cross-linking.In contrast to SLP-76, BLNK did not require Grb2 families for its recruitment to GEMs. (nih.gov)
  • The ELISA analytical biochemical technique of the MBS008014 kit is based on GRB2 antibody-GRB2 antigen interactions (immunosorbency) and an HRP colorimetric detection system to detect GRB2 antigen targets in samples. (mybiosource.com)
  • This network of protein-protein interactions may reflect the ability of the Shc/Grb-2 pathway to act as a molecular switch controlling different cellular functions regulated by RTK activation. (nih.gov)
  • The pathway maps illustrate protein interactions and regulation to provide a comprehensive picture of signaling and disease processes. (bio-rad.com)
  • however, when fused to BCR, the oncoprotein loses this property and is mainly retained within the cytoplasm, where it interacts with the majority of proteins involved in the oncogenic pathway. (aacrjournals.org)
  • and tests of cell autonomy and epistasis frequently position the requirement for the protein in the pathway, even before its biochemical activity is known. (springer.com)
  • Other candidates that have emerged as possible components of the ethylene signal transduction pathway are monomeric GTP-binding proteins (monomeric G-proteins). (plantphysiol.org)
  • Bongartz H, Gille K, Hessenkemper W, Mandel K, Lewitzky M, Feller SM, Schaper F (2019) The multi-site docking protein Grb2-associated binder 1 (Gab1) enhances interleukin-6-induced MAPK-pathway activation in an SHP2-, Grb2-, and time-dependent manner. (uni-halle.de)
  • Exploiting this fact, we have developed proximity ligation assays (PLA) to annotate protein complexes reflecting an activated EGFR, a key RTK in lung cancer and other cancers. (aacrjournals.org)
  • We show that PLA can be developed starting with mass spectrometry based protein-protein interaction datasets to characterize in situ EGFR complexes reflecting active signaling in cancer tissues. (aacrjournals.org)
  • We have developed one such assay reflecting EGFR in complex with its adaptor protein GRB2. (aacrjournals.org)
  • We demonstrate feasibility and utility in characterizing EGFR:GRB2 complexes in nearly 300 patient derived xenograft models of cancer. (aacrjournals.org)
  • In both the PDX and patient cohorts, high EGFR:GRB2 signal by PLA is associated with responsiveness to anti-EGFR therapy. (aacrjournals.org)
  • EGF stimulates lacrimal gland secretion of protein by activating the EGFR to increase [Ca 2+ ] i and activate PKC. (arvojournals.org)
  • Activated EGFR recruits various cytoplasmic proteins which transduce and regulate the EGFR function. (wikipathways.org)
  • GRB2 or other adaptor proteins such as GABs recruits PI3Ks, another major mediator of EGFR signaling. (wikipathways.org)
  • EGFR also translocates from the plasma membrane to other cellular compartments including nucleus where it directly regulate the expression of several genes in cooperation with other transcriptional regulators such as STATs, PCNA and E2F family of proteins. (wikipathways.org)
  • There are several proteins which have been reported to regulate the EGFR signaling such as CBL, CSK, PKC and PTEN which promotes endocytosis or reduction in the EGFR activity or its signaling mediators. (wikipathways.org)
  • The MA5-13319 immunogen is extracellular domain of human recombinant EGFR protein. (thermofisher.com)
  • Mutations in the EGFR gene are associated with lung cancer and multiple alternatively spliced transcript variants encode different protein isoforms of EGFR have been found. (thermofisher.com)
  • The adaptor protein Grb2 (GRB2) and the guanine nucleotide exchange factor Sos1 (SOS) are recruited to the membrane, binding to EgfR. (coursehero.com)
  • We addressed these issues by investigating the translocation of the adaptor protein Shc to the epidermal growth factor receptor (EGFR, erbB1), locally activated with epidermal growth factor (EGF)-coated microspheres. (biologists.org)
  • Check out links to articles that cite our custom service antibodies, peptides, and proteins in major peer-reviewed journals, organized by research category. (abgent.com)
  • Background: Normal Rabbit IgG is an isotype control antibody, which is used to estimate the non-specific binding of target primary antibodies due to Fc receptor binding or other protein-protein interactions. (cellsignal.com)
  • This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometry and immunofluorescent analysis in cells transfected with Myc-tagged protein. (cellsignal.com)
  • To date, I have published 122 research papers and 36 review articles and have co-edited a book on antibody fusion proteins. (gene.com)
  • Rabbit polyclonal anti-hemagglutinin (HA) antibody from Babco (Richmond, CA) was used to detect HA-tagged proteins. (pnas.org)
  • This gene encodes a member of the GRB2/Sem5/Drk family and functions as a cytoplasmic signaling protein which contains an SH2 domain flanked by two SH3 domains. (antibodies-online.com)
  • The ability of these sequences to act as SH3 domain recognition motifs was investigated using bacterially expressed SH3 domains derived from several different signalling proteins. (nih.gov)
  • These interaction domains exist in the natural tertiary structure of proteins. (jci.org)
  • In other cases, the domains for interaction are created by posttranslational covalent modification of the protein. (jci.org)
  • PH domains, which are found in most of the proteins that interact with the insulin receptor, bind to charged headgroups of specific phosphatidylinositides and are thereby targeted preferentially to membrane structures. (jci.org)
  • p130Cas/BCAR1 is a scaffold protein characterized by several structural domains. (wikipedia.org)
  • The Grb2 SH3 domains bind proline-rich motifs in SOS, the guanine nucleotide exchange factor for Ras, recruiting SOS to the membrane and colocalizing it with Ras. (sciencemag.org)
  • The animation could be useful in demonstrating how different protein domains allow dynamic regulation of protein activity, protein assembly, and protein recruitment, allowing cells to respond to signals from their extracellular environment. (sciencemag.org)
  • Similar to related family member, GRB2-related adaptor protein contains an SH2 domain flanked by two SH3 domains and it interacts with other proteins, for example GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. (prospecbio.com)
  • Like its related family member, GRB2-related adaptor protein (GRAP), this protein contains an SH2 domain flanked by two SH3 domains. (abnova.com)
  • This protein interacts with other proteins, such as GRB2-associated binding protein 1 (GAB1) and the SLP-76 leukocyte protein (LCP2), through its SH3 domains. (abnova.com)
  • A family of SH2 and SH3 domain-containing proteins, including Crk, Grb2, and Nck, contain only SH2 and SH3 domains and have no other functional motifs ( 2 , 19 ). (asm.org)
  • They act by binding to tyrosine-phosphorylated proteins via SH2 domains and associating with P-X-X-P motif-containing proteins through SH3 domains. (asm.org)
  • The human genome encodes 120 SH2 domains embedded in a variety of proteins ( Fig. 1A ). (sciencemag.org)
  • Our understanding of the regulation of biological processes by protein interactions has been significantly enhanced by the description of modular binding domains and their preferred target sequences ( 1 , 2 ). (pnas.org)
  • Since its identification as a Cbl-interacting protein, CIN85 has been found to interact with many molecular partners through its SH3 domains, a proline-rich region, and a coiled-coil domain ( Fig. 1 ). (diabetesjournals.org)
  • It has been previously shown by mutagenesis studies that the specificity of G protein coupling for βAR is dictated by the intracellular domains, particularly the third intracellular loop and the C-terminal tail ( 7 , 8 ). (pnas.org)
  • These IGFBPs share a highly conserved protein domain structure consisting of three main parts (N, L, and C domains). (biomedcentral.com)
  • These intracellular protein-protein interactions are pivotal in transmitting the signal from the receptor to the final cellular effect, such as translocation of vesicles containing GLUT4 glucose transporters from the intracellular pool to the plasma membrane, activation of glycogen or protein synthesis, and initiation of specific gene transcription (Figure 1 ). (jci.org)
  • CREB was originally isolated as a gene regulatory protein that bound to the CRE site of the somatostatin gene promoter region in response to an increase in the cellular cAMP level. (ahajournals.org)
  • Given the ability of p130Cas/BCAR1 scaffold protein to convey and integrate different type of signals and subsequently to regulate key cellular functions such as adhesion, migration, invasion, proliferation and survival, the existence of a strong correlation between deregulated p130Cas/BCAR1 expression and cancer was inferred. (wikipedia.org)
  • Growth factor receptor-bound protein 2 (Grb2) is an adaptor protein that plays a critical role in cellular signal transduction. (rcsb.org)
  • The second messengers of PIs are associated with major cellular functions such as growth, differentiation, apoptosis, protein trafficking, and motility. (hindawi.com)
  • Information relay from one cellular location to another often requires the dynamic formation of protein complexes. (sciencemag.org)
  • 70 cellular proteins were found to be associated with (4) . (who.int)
  • Most recently, our lab has been studying the mechanisms that mediate apoptosis activation in response to cellular stress caused by DNA damage or protein misfolding. (gene.com)
  • replacing Arg βB5, located at the base of the pocket, with a Lys or other residues drastically affects the ability of activated c-Abl proteins and Bcr/Abl proteins to transform immortalized fibroblast lines ( 1 , 28 ). (asm.org)
  • The IGFBP-5 protein contains 18 conserved cysteine residues, of which 12 are located in the N-terminal domain and the others in the C-terminal domain. (biomedcentral.com)
  • Both Itk and Lck are able to phosphorylate the tyrosine residues which then allow binding of SH2 containing proteins to CD28. (wikidoc.org)
  • This protein also associates with the Ras guanine nucleotide exchange factor SOS1 (son of sevenless homolog 1) through its N-terminal SH3 domain. (antibodies-online.com)
  • For example, when activated by SRC , the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to translocate to the Golgi apparatus , where it activates Ras. (wikipedia.org)
  • Prototypically, the growth factor receptor on activation recruits a Ras guanine nucleotide exchange factor (GEF), Sos, via adaptor proteins Shc and Grb2. (ahajournals.org)
  • This causes adaptor protein GRB2 to recruit SOS, a guanine nucleotide exchange factor, which then facilitates binding of GTP to Ras. (biolegend.com)
  • p130Cas/BCAR1 is a member of the Cas family (Crk-associated substrate) of adaptor proteins which is characterized by the presence of multiple conserved motifs for protein-protein interactions, and by extensive tyrosine and serine phosphorylations. (wikipedia.org)
  • This activation process depends mainly on CD3 (Cluster of Differentiation 3), a multiunit protein complex that directly associates with the TCR. (cellsignal.com)
  • These Grb2 floxed mice may be useful for studying the effect of GRB2-dependant signal transduction on lymphocyte differentiation and immune response. (jax.org)
  • For example, when crossed to a strain expressing a B-cell specific Cre recombinase, GRB2 deficient mice have reduced numbers of immature and mature follicular B cells in peripheral lymphoid organs due to a differentiation block and decreased B-cell survival. (jax.org)
  • As in other multicellular organisms, RAS proteins play a key role in the signaling pathways that regulate cell growth and differentiation in Drosophila . (springer.com)
  • CD28 (Cluster of Differentiation 28) is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. (wikidoc.org)
  • p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence. (uniprot.org)
  • Thus, p60src plays a critical role in the shear stress activation of MAPK pathways and induction of Activating Protein-1 (AP-1)/TRE and Elk-1/SRE-mediated transcription in ECs. (ahajournals.org)
  • Of particular note is the transmembrane adaptor protein LAT which is preferentially associated with rafts due to its palmitoylation ( 29 , 30 ). (rupress.org)
  • Here we show that SCIMP, an immune-restricted, transmembrane adaptor protein (TRAP), promotes selective proinflammatory cytokine responses by direct modulation of TLR4. (nature.com)
  • This gene encodes a member of the GRB2/Sem5 (C. elegans homolog)/Drk (Drosophila homolog) family. (wikipedia.org)
  • The lin-3 gene encodes a protein similar to epidermal growth factor (EGF) that is the inductive signal secreted by the anchor cell ( H ill and S ternberg 1992 ). (genetics.org)
  • Exon 2 encodes part of the first SH3 domain and its deletion leads to a non-functional GRB2 protein. (jax.org)
  • This gene, which has four exons, encodes a soluble protein of approximately 29 kDa expressed in various types of tissues in humans. (biomedcentral.com)
  • TNF-α strongly activates NF-κB through a second class of adaptor protein TNFR-associated factors, and this transcriptional factor regulates the expression of antiapoptotic gene products ( 6 , 7 , 8 ), such as antiapoptotic members of the Bcl-2 family ( 9 ) and the inhibitor of apoptosis proteins (IAP) 3 c-IAP1 and c-IAP2 ( 10 ). (jimmunol.org)
  • it has been shown that ethylene at physiological concentrations activates monomeric G-proteins. (plantphysiol.org)
  • GRB2 (Growth Factor Receptor Bound Protein 2) is a Protein Coding gene. (genecards.org)
  • The name Grb2 is an abbreviation of Growth factor receptor-bound protein 2. (wikidoc.org)
  • These Grb2 floxed mice possess loxP sites flanking exon 2 of the growth factor receptor bound protein 2 ( Grb2 ) gene. (jax.org)
  • The adaptor protein growth factor receptor-bound protein 2 (Grb2), was found to be upregulated in HCMV-infected cells and play as crucial role in cancer progression. (who.int)
  • MBS008014 is a ready-to-use microwell, strip-or-full plate Sandwich ELISA (enzyme-linked immunosorbent assay) Kit for analyzing the presence of the Growth Factor Receptor Bound Protein 2 (GRB2) ELISA Kit target analytes in biological samples. (mybiosource.com)
  • The BCR-ABL/GRB2 complex recruits Son of Sevenless (SOS), which is constitutively associated with the GRB2 SH3 domain ( 10 ). (aacrjournals.org)
  • Experimental detection of short regulatory motifs in eukaryotic proteins: tips for good practice as well as for bad. (ebi.ac.uk)
  • Thus, our studies demonstrate a role of the SH3p4/p8/p13 protein family in β1-AR signaling and suggest that interaction between proline-rich motifs and SH3-containing proteins may represent a previously underappreciated aspect of G-protein coupled receptor signaling. (pnas.org)
  • CD28 also contains two proline -rich motifs that are able to bind SH3 -containing proteins. (wikidoc.org)
  • Accordingly, we used the proline-rich third intracellular loop of the β1-AR either as a glutathione S -transferase fusion protein in biochemical "pull-down" assays or as bait in the yeast two-hybrid system to search for interacting proteins. (pnas.org)
  • To determine the effects of epidermal growth factor (EGF) on lacrimal gland secretion of proteins and characterize its signal-transducing components. (arvojournals.org)
  • Currently, about 100 specialized protein-interaction modules have been identified that recognize a plethora of chemical signals. (sciencemag.org)
  • In the absence of a WNT-Frizzled low density lipoprotein receptor-related protein-5/6 co-receptor interaction (WNT-FZD-LRP5/6), β-catenin is caught in a molecular destruction complex, phosphorylated and degraded by the proteasome. (biomedcentral.com)
  • In an attempt to better understand the biology of β1-AR signaling and the molecular determinants underlying the differences between β1-AR and β2-AR regulation, we set out to search for novel binding proteins for the β1-AR by using its third intracellular loop as bait in several protein interaction systems. (pnas.org)
  • The cAMP response element binding protein (CREB) is a ubiquitously expressed nuclear transcription factor that is activated by various extracellular stimuli. (ahajournals.org)
  • Grb2 as a cytoplasmic adaptor protein that and its incidence is higher among African-American associated with activated epidermal growth factor compared to white women (3) . (who.int)
  • Abgent has over fifteen years of experience producing recombinant proteins in E. coli and mammalian cells (CHO and HEK293, etc), and we have added a powerful yeast expression platform to our menu of services. (abgent.com)
  • In cases where a mutation caused Trp121 to be replaced by Ser in Grb2 SH2, this protein still formed dimers, but lost the ability to bind CD28. (rcsb.org)
  • Can bind to GRB2 adapter protein. (merckmillipore.com)
  • IGFBPs may interact with proteins other than IGFs, may be cleaved, may bind to their own receptor on the membrane, and may locate both extracellularly and intracellularly [ 11 ]. (biomedcentral.com)
  • We have also found that SIT negatively regulates BCR-mediated signals in B1 B cells and shares overlapping function with the transmembrane adaptor LAX to regulate the number of B1 B cells. (forschung-sachsen-anhalt.de)
  • PDK1 phosphorylates AKT which in turn regulate the activity of various proteins that mediate cell survival. (wikipathways.org)
  • IGFBPs are traditionally known as carrier proteins that regulate the activity of IGFs by prolonging their half-life and their circulation turnover [ 4 ]. (biomedcentral.com)
  • Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed. (uniprot.org)
  • section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. (uniprot.org)
  • Consistent with the idea that signals requiring an intact SH2 domain pass through Ras and lead to c-Myc ( 52 ), transformation of RAT-1 cells by Bcr/Abl proteins containing an altered FLVRES motif is complemented by expression of c-Myc ( 1 , 25 ). (asm.org)
  • The animation shows a schematic representation of the assembly role of SH3 domain-containing proteins using Grb2 as an example. (sciencemag.org)
  • The resultant phosphotyrosines form docking sites for the adaptor protein Grb2 (through its SH2 domain). (sciencemag.org)
  • This complex between the Abl SH3 domain, Crk SH2 domain, and Crk phosphopeptide is an example of the extremely modular nature of regulatory proteins that provides a rich repertoire of mechanisms for control of biological function. (pnas.org)
  • Binding of TNF-α to TNFR-1 (p55) results in trimerization of its C-terminal cytoplasmic "death domain" and recruitment of some intracellular proteins involved in apoptotic signal transduction ( 2 , 3 , 4 ). (jimmunol.org)
  • SCIMP is a non-TIR-containing adaptor, binding directly to the TLR4-TIR domain in response to lipopolysaccharide. (nature.com)
  • Both approaches identified SH3p4/p8/p13 (also referred to as endophilin 1/2/3), a SH3 domain-containing protein family, as binding partners for the β1-AR. (pnas.org)
  • PH domain and leucine rich repeat protein. (broadinstitute.org)
  • The protein is anchored to the apical surface of many epithelia by a transmembrane domain, with the degree of glycosylation varying with cell type. (merckmillipore.com)
  • Domain structure of insulin-like growth factor binding protein 5 and potential functional effects. (biomedcentral.com)
  • The MUC1-C cytoplasmic domain also contains a YTNP site that, when tyrosine phosphorylated, interacts directly with the SH2 domain of the Grb2 adapter protein ( 21, 22 ). (aacrjournals.org)
  • Our results show that FAK functions as a key regulator of fibronectin receptor stimulated cell migration events through the recruitment of both SH2 and SH3 domain-containing signaling proteins to sites of integrin receptor clustering. (biologists.org)
  • Overexpression, aberrant intracellular localization, and changes in glycosylation of this protein have been associated with carcinomas. (merckmillipore.com)
  • Shc can complex with Grb2 and the G-protein exchange factor, mSos, facilitating the activation of Ras ( 14 , 27 ). (asm.org)
  • The DD is important for transducing the death signal by recruiting other DD containing adaptor proteins (FADD, TRADD, RIP) to the death-inducing signaling complex (DISC), resulting in activation of caspases. (cellsignal.com)
  • these adaptors facilitate activation of the MyD88-dependent and TRIF-dependent pathways. (jimmunol.org)
  • The protein SRC is a key player in the activation of various pathways such as RAS, PLC and also the STAT proteins in various cells. (wikipathways.org)
  • Autoinhibition release involves structural rearrangements of the protein at the membrane and thus introduces a delay between initial recruitment and activation. (stanford.edu)
  • For monomeric G-proteins, the effect may be a rapid (2 min) and bimodal up-regulation, a transiently unimodal activation, or a transient down-regulation. (plantphysiol.org)
  • High-resolution confocal microscopy of a fusion construct of the receptor and the green fluorescent protein expressed in Chinese hamster ovary cells demonstrated that engulfment and internalization of the microspheres occurred rapidly within minutes, and in a receptor activation-dependent manner. (biologists.org)
  • Diseases associated with GRB2 include Hepatitis C and Hepatitis E . Among its related pathways are Association Between Physico-Chemical Features and Toxicity Associated Pathways and Common Cytokine Receptor Gamma-Chain Family Signaling Pathways . (genecards.org)
  • In this review, we describe detailed mechanisms of signal transduction pathways of Ang II involving small G proteins in VSMCs together with their functional significances in mediating vascular remodeling. (ahajournals.org)
  • It was also shown that shear stress differentially regulates JNK and ERK by signaling that involves PTx-insensitive G protein-dependent and G i2 -dependent pathways, respectively. (ahajournals.org)
  • Belongs to the GRB2/sem-5/DRK family. (abcam.com)
  • p130Cas/BCAR1 belongs to the Cas family of adaptor proteins and can act as a docking protein for several signalling partners. (wikipedia.org)
  • The Cas family comprises other three members: NEDD9 (Neural precursor cell expressed, developmentally down-regulated 9, also called Human enhancer of filamentation 1, HEF-1 or Cas-L), EFS (Embryonal Fyn-associated substrate), and CASS4 (Cas scaffolding protein family member 4). (wikipedia.org)
  • PP1 and PP2 are the most abundant and ubiquitous serine/threonine protein phosphatases in this family. (hindawi.com)
  • In this context, a family of immune cell specific adaptor proteins have been identified in recent years ( 26 - 28 ). (rupress.org)
  • Src homolog and collagen homolog 3 (Shc3) is an adaptor protein belonging to the Shc family. (nature.com)
  • Other members of the TLR family also couple with TIR-containing adaptors at the cell surface or in endosomes to generate specificity in signalling responses. (nature.com)
  • This gene is a member of the GRB2-associated binding protein (GAB) gene family. (thermofisher.com)
  • The family of insulin-like growth factor binding proteins (IGFBPs) has been shown to have a diverse spectrum of functions in cell growth, death, motility, and tissue remodeling. (biomedcentral.com)
  • GRB2-related adapter protein is a protein that in humans is encoded by the GRAP gene. (wikipedia.org)
  • Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the BCAR1 gene. (wikipedia.org)
  • Phospholipase C, gamma 1 , also known as PLCG1 , is a protein that in humans is encoded by the PLCG1 gene . (wikipedia.org)
  • 100 small G proteins have been identified in eukaryotes from yeast to humans. (ahajournals.org)
  • Mice deficient in GDNF, GFRα1 or the RET protein itself exhibit severe defects in kidney and enteric nervous system development. (wikipedia.org)
  • RESEARCH DESIGN AND METHODS We used RNA and chromatin from insulin-treated rat hepatic tumor cell line expressing human insulin receptor (HTC-IR) and livers from lean and insulin-resistant ob/ob glucose-fed mice in quantitative RT-PCR and chromatin immunoprecipitation studies to determine gene expression levels and associated recruitment of RNA polymerase II (Pol II), insulin receptor, and cognate signaling proteins to gene loci, respectively. (diabetesjournals.org)
  • The aim of this research was to study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled-related protein (Frzb) compared to wild-type mice by transcriptome analysis. (biomedcentral.com)
  • In contrast to SLP-76, BLNK did not require Grb2 families for its recruitment to GEMs. (nih.gov)
  • Recombinant human GRAP protein expressed in HEK293 cells. (antibodies-online.com)
  • Recombinant Human GRB2 protein ( ab85917 ) can be used as a positive control in WB. (abcam.com)
  • This work opens up the human protein interactome as a new class of molecular markers for disease in a more practical manner. (aacrjournals.org)
  • Trapping Grb2 within immune cells: the role. (forschung-sachsen-anhalt.de)
  • RESULTS Insulin-induced egr-1 mRNA in HTC-IR cells was associated with corecruitment of IR signaling cascade (IR, SOS, Grb2, B-Raf, MEK, and ERK) to this gene. (diabetesjournals.org)
  • The GP precursor is post-translationally cleaved by the pro-protein convertase furin within the Golgi compartment of virus-producer cells, yielding two disulfide-linked subunits, GP1 and GP2 [ 13 ]. (mdpi.com)
  • It mostly develops as a result of dysregulated insulin signaling in insulin-sensitive cells, as compared to inactivating mutations in insulin receptor or signaling proteins that occur relatively rare. (hindawi.com)
  • Binding of Grb2 SH2 to the cytoplasmic region of CD28, phosphorylated Tyr (pY) containing the peptide motif pY-X-N-X, is required for costimulatory signaling in T cells. (rcsb.org)
  • Protein secretion by the mammalian lacrimal gland is primarily a function of the acinar cells, which are highly polarized cells constituting the main cell type in the lacrimal gland, 3 and is regulated by neurotransmitters released from sympathetic and parasympathetic nerves. (arvojournals.org)
  • This was confirmed biochemically where CD28 augmented the detection of the adaptor LAT in purified rafts, while CTLA-4 coligation blocked this increase at the level of resting T cells. (rupress.org)
  • However, TIR-containing adaptor proteins are widely expressed, and additional mechanisms or adaptors that enable either heightened or more selective inflammatory responses in innate immune cells are not well understood. (nature.com)