• GRB2 Adaptor Protein" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uchicago.edu)
  • This graph shows the total number of publications written about "GRB2 Adaptor Protein" by people in this website by year, and whether "GRB2 Adaptor Protein" was a major or minor topic of these publications. (uchicago.edu)
  • Below are the most recent publications written about "GRB2 Adaptor Protein" by people in Profiles. (uchicago.edu)
  • GRB2 (growth factor receptor-bound protein 2), an adaptor protein involved in signal transduction, contains a central SH2 domain flanked by two SH3 domains. (rndsystems.com)
  • Validation experiments with knockdown of GAB2 and Far-Western blots proved the direct interaction of SHP2 with p85, independent of adaptor proteins and transfected FLAG-p85 provided evidence that SHP2 binding on p85 occurred on the SH2 domains. (sdbonline.org)
  • Receptor dimerization and autophosphorylation attracts proteins containing Src homology 2 (SH2) or phosphotyrosine binding (PTB) domains including adaptor proteins like FRS2 and GRB2. (springer.com)
  • BACKGROUND The Src tyrosine kinase substrate and adaptor proteins Tks5 had previously been implicated in the invasive phenotype of normal and transformed cell types via rules of cytoskeletal constructions called podosomes/invadopodia. (healthanddietblog.info)
  • Tks5 is a substrate of Src and an adaptor protein for proteins and lipids [19]. (healthanddietblog.info)
  • The Grb2-like adaptor protein Mona/Gads associates stably with the T-cell receptor signal transducer SLP-76. (ox.ac.uk)
  • Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. (bvsalud.org)
  • We overexpress and purify adaptor proteins, Growth factor receptor bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), phosphatidylinositol-3 kinase (PI3K), and their SH2 domains, and analyze their molecular interactions with the intracellular regions of CD28, ICOS, and CTLA-4. (kpu-biophyschem.com)
  • Here, we show that insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains. (nih.gov)
  • Endophilin-A2, SH3 domain protein 2B or SH3 Domain-Containing GRB2-Like Protein 1 is encoded by the gene Sh3gl1 and a member of the endophilin family of Src homology 3 domain-containing proteins. (antibodiesinc.com)
  • The SH2 domain binds to phosphotyrosine residues in RTKs such as PDGF and EGF, non-RTKs such as Bcr/Abl and FAK, and docking proteins such as FRS-2 and Gab1. (rndsystems.com)
  • A fly-human cross-species comparison of the phosphoinositide-3-kinase (PI3K) interactome was conducted in a Drosophila S2R+ cell line and several NSCLC and human multiple myeloma cell lines to identify conserved interacting proteins to PI3K, a critical signaling regulator of the AKT pathway. (sdbonline.org)
  • Src Homology 2 (SH2) domains are small modular domains found within a great number of proteins involved in different signalling pathways. (eu.org)
  • Mutations identified in many SH2 domain-containing proteins as well as the SH2 domain itself are associated with human diseases ranging from cancers, diabetes, to immunodeficiencies. (eu.org)
  • SH2 domains are phosphotyrosine recognition domains, often mediating transient interactions with target proteins. (eu.org)
  • CONCLUSIONS Our outcomes suggest an over-all part for Src-Tks5 signaling in prostate tumor development and the energy of Tks5 like a marker proteins for the staging of the disease. (healthanddietblog.info)
  • Tumor cell motility and extracellular matrix SAT1 degradation are backed by cytoskeletal constructions known as invadopodia [2 3 Invadopodia as well as the related podosomes of regular cell types are actin-based cell surface area protrusions that enable adherence to and degradation of extracellular matrix proteins. (healthanddietblog.info)
  • Src activation also frequently promotes podosome/invadopod development [4 11 That is backed by the current presence of tyrosine phosphorylated proteins at these constructions many of that are Src substrates [14-18]. (healthanddietblog.info)
  • Therefore, FAK-Src signaling complicated activates a great many other signaling proteins, involved with success, motility and metastatic, intrusive phenotype in tumor cells. (cahrr.org)
  • An important consequence of reversible phosphorylation of tyrosine residues on proteins is the creation of binding sites for phosphotyrosine recognizing domains such as Src homology 2 (SH2) and phosphotyrosine binding (PTB) domains [ 1 , 2 ]. (biomedcentral.com)
  • Domain commonly found in eukaryotic signalling proteins. (embl.de)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • Through these interactions, PH domains play a role in recruiting proteins to different membranes, thus targeting them to appropriate cellular compartments or enabling them to interact with other components of the signal transduction pathways. (embl.de)
  • Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
  • Regulators of small G-proteins like guanine nucleotide releasing factor GNRP (Ras-GRF) (which contains 2 PH domains), guanine nucleotide exchange proteins like vav, dbl, SoS and Saccharomyces cerevisiae CDC24, GTPase activating proteins like rasGAP and BEM2/IPL2, and the human break point cluster protein bcr. (embl.de)
  • Cytoskeletal proteins such as dynamin (see IPR001401 ), Caenorhabditis elegans kinesin-like protein unc-104 (see IPR001752 ), spectrin beta-chain, syntrophin (2 PH domains) and S. cerevisiae nuclear migration protein NUM1. (embl.de)
  • There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing PH domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with PH domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing PH domain in the selected taxonomic class. (embl.de)
  • Hyaluronan-mediated CD44 interaction with RhoGEF and Rho kinase promotes Grb2-associated binder-1 phosphorylation and phosphatidylinositol 3-kinase signaling leading to cytokine (macrophage-colony stimulating factor) production and breast tumor progression. (uchicago.edu)
  • The Src Homology 2 (SH2) domain is a major protein interaction module that is central to tyrosine kinase signaling. (eu.org)
  • This Tks5-reliant increase in intrusive behavior additional depended on Src tyrosine kinase activity as well as the phosphorylation of Tks5 at tyrosine residues 557 and 619. (healthanddietblog.info)
  • Src is generally upregulated in advanced stage malignancies and activation of Src tyrosine kinase activity transforms cells to a neoplastic phenotype with improved survival development and migration [8-10]. (healthanddietblog.info)
  • FAK gets the N-terminal, Kinase site as well as the C-terminal domains. (cahrr.org)
  • Phosphorylated Y397 FAK can recruit another essential signaling protein, p85 PI3-kinase (phosphoinositide 3-kinase), development factor receptor destined protein Grb 7, phospholipase Cgamma(PLCgamma) and. (cahrr.org)
  • Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. (embl.de)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • CD28 enhances TCR-driven tyrosine phosphorylation and interacts with phosphatidylinositol 3-kinase (PI3K) and Grb2, initiating the Akt-mTOR and Ras-MAPK pathways. (medicaltrend.org)
  • Physiologically, the N-terminal domain of p126 binds the Src-homology 3 (SH3) domain of c-Abl, leading to activation of the MAPK/ERK2 kinase. (molcells.org)
  • The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. (cancerindex.org)
  • Previous studies have demonstrated that DNA damage-inducible transcript 4 (DDIT4), Trib3 (tribbles pseudo kinase 3), alpha-synuclein (α-syn) are involved in METH-induced dopaminergic neurotoxicity. (cancerindex.org)
  • Kinetics of Src homology 3 domain association with the proline-rich domain of dynamins: specificity, occlusion, and the effects of phosphorylation. (uchicago.edu)
  • Tyrosine phosphorylation of GRB2 SH3 domains reduces binding to Sos and negatively regulates downstream signaling pathways including Ras, JNK and MAPK. (rndsystems.com)
  • In Personal computer-3 cells we proven that Tks5 phosphorylation at these websites was required and adequate for invadopodia-associated matrix degradation and invasion. (healthanddietblog.info)
  • Tks5 has Src phosphorylation sites located between your fourth and third SH3 domains [19]. (healthanddietblog.info)
  • We while others possess proven that Tks5 phosphorylation can be important for podosome development and associated matrix degradation in macrophages and osteoclasts [24 25 In melanoma cells Src-dependent phosphorylation of Tks5 at tyrosine 557 is important for binding to Nck for Nck recruitment to invadopodia and for invadopodia-associated matrix degradation activity [16]. (healthanddietblog.info)
  • We previously established SH2 profiling, a phosphoproteomic approach based on membrane binding assays that utilizes purified Src Homology 2 (SH2) domains as a molecular tool to profile the global tyrosine phosphorylation state of cells. (biomedcentral.com)
  • SH2 profiling is a unique proteomic method in which interactions between an array of SH2 domains and protein samples are quantitatively analyzed, thereby defining the functional output of tyrosine phosphorylation. (biomedcentral.com)
  • These two levels serve degraded by a phosphorylation including at least 6 membranes in a such tail that both leaves the 2' disorder ubiquitination and adducts the 3' heart to the 5' cell. (evakoch.com)
  • In contrast to the activated epidermal growth factor receptor that binds the GRB2-Sos complex directly, activation of the insulin receptor results in the interaction of GRB2-Sos with IRS-1 and Shc, thus linking the insulin receptor to Ras signaling pathways. (nih.gov)
  • the preferred GFRα coreceptor for GDNF is GFRα1, although GDNF also weakly binds to GFRα2 and GFRα3 [ 3 ]. (medsci.org)
  • The Tir protein of EPEC binds NCK1/NCK2 SH2 domains through a high affinity pYDEV motif ( Frese,2006 ). (eu.org)
  • These motifs are phosphorylated by Src family kinases (SFKs) upon receptor activation and play crucial roles in regulating the immune system. (medicaltrend.org)
  • The assay detected signal across at least 3 orders of magnitude of lysate input with a linear range spanning 1-2 orders and a low femtomole limit of detection for EGFR phosphotyrosine. (biomedcentral.com)
  • Interestingly, the SH3C displays ion-dependent dimerization in the crystal and in solution, suggesting a novel mechanism for the regulation of SH3 domain functions. (ox.ac.uk)
  • The mechanism of host cell invasion by SARS-CoV-2 involves the interaction of angiotensin-converting enzyme (ACE2) with receptor-binding domain (RBD) of spike protein (S). The main protease (Mpro/3CLpro) is an attractive drug target due to its vital function in regulation of polyprotein translated from viral RNA. (bvsalud.org)
  • Regions outside of conserved PxxPxR motifs drive the high affinity interaction of GRB2 with SH3 domain ligands. (uchicago.edu)
  • Hyaluronan promotes CD44v3-Vav2 interaction with Grb2-p185(HER2) and induces Rac1 and Ras signaling during ovarian tumor cell migration and growth. (uchicago.edu)
  • The interaction between SH2 domains and their substrates is however dependent also on cooperative contacts of other surface regions. (eu.org)
  • AT-rich interaction domain 5B [Source:HG. (gsea-msigdb.org)
  • The p85-SHP2 association was validated in human cell lines, and formed a ternary regulatory complex with GRB2-associated-binding protein 2 (human GAB2 but not Drosophila Dos ). (sdbonline.org)
  • Noonan syndrome (NS) and NS with multiple lentigines (NSML) cognitive dysfunction are linked to SH2 domain-containing protein tyrosine phosphatase-2 (SHP2) gain-of-function (GoF) and loss-of-function (LoF), respectively. (sdbonline.org)
  • Oncogenic protein tyrosine phosphatases have long been viewed as drug targets of interest, and recently developed allosteric inhibitors of SH2 domain-containing phosphatase-2 (SHP2) have entered clinical trials. (aacrjournals.org)
  • Though they talk about a number of the same cytoskeletal regulatory equipment (integrins tyrosine kinases Arp2/3 WASp) as additional adhesion constructions they are recognized by marker protein CK-1827452 (Omecamtiv mecarbil) (cortactin dynamin2 Tks5) and metalloproteinases (MT1-MMP) that distinctively support focalized matrix redesigning activity [2-5]. (healthanddietblog.info)
  • Src may be the namesake person in a grouped category of non-receptor tyrosine kinases as well as the initial described protooncogene [7]. (healthanddietblog.info)
  • The TSEN placement Typically triggers 5' and 3' to the home', proliferating a downstream' vascular maturation on the 5' T and a 5' receptor nucleus on the 3' mitosis. (evakoch.com)
  • The SH3 domains associate with proline rich motifs on the guanine nucleotide releasing factor, Sos, stimulating GTP binding to Ras, which in turn activates MAPK and other signaling pathways. (rndsystems.com)
  • Several different binding motifs are known, for example: pYEEI (Src-family SH2 domains), pY [IV]. (eu.org)
  • The C-terminal half of the SH2 domain exhibits greater structural variability and provides a platform for accommodating different kinds of SH2-binding motifs. (eu.org)
  • In addition, ST5 enhanced activation of Src and Syk, a Src substrate, in response to RANKL. (molcells.org)
  • GRB2 overexpression led to increased formation of a complex between the guanine nucleotide-releasing factor Sos (the product of the mammalian homolog of son of sevenless gene) and GRB2. (nih.gov)
  • Val and Pro confer high-affinity binding at pY+3 - Ala and Ile are tolerated but confer weaker binding. (eu.org)
  • Structural basis for SH3 domain-mediated high-affinity binding between Mona/Gads and SLP-76. (ox.ac.uk)
  • The central R-x-x-K motif of the peptide forms a 3(10) helix and inserts into a negatively charged double pocket on the SH3C while several other residues complement binding through hydrophobic interactions, creating a short linear SH3C binding epitope of uniquely high affinity. (ox.ac.uk)
  • Based on the amino acid sequence homology and biological activity in macrophages, Shimamoto et al ( 15 ) identified that HLP was identical to MSP ( 15 ). (spandidos-publications.com)
  • The aim of this study was to investigate the diversity of cagA 3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region of H. pylori , and their association with gastroduodenal diseases. (biomedcentral.com)
  • Pleckstrin homology domain. (embl.de)
  • The N-terminal site (1C415 a.a) of FAK protein provides the main autophosphorylation site Con397-tyrosine, that in phosphorylated form becomes a binding site of SH-2 site of Src, resulting in its conformational adjustments and activation (19). (cahrr.org)
  • Different families of SH2 domains may have different binding specificity, which is usually determined by a few residues C-terminal with respect to the pY (positions +1 to +4). (eu.org)
  • The human NCK1 (Nckα) and NCK2 (Nckβ/GRB4) SH2 domains show a degree of partner specificity but share the same mode of ligand binding ( Frese,2006 ) and belong to the class IA family which contains an aromatic residue (Phe) at the specificity-determining βD5 position ( Kaneko,2010 ). (eu.org)
  • The other two positions important for binding are pY+3 and pY+1. (eu.org)
  • In NCK SH2 domains, the EF loop is positioned away from the BG loop, exposing the pY+3 binding pocket where the side chain of Val forms tight interactions. (eu.org)
  • The binding affinity of an SH2 domain to a pTyr containing ligand is moderate, with the typical affinity range between 0.1 µМ to 10 µМ for equilibrium dissociation constant values (Kd) ( Kaneko,2012 ). (eu.org)
  • Three loops surround the peptide binding pocket and are important for specificity: Because these loops can be flexible, considerable variation in peptide binding can apply for any given SH2 domain. (eu.org)
  • Alternate mRNA splicing gives rise to two distinct forms (b and c) of FGFRs1-3 which differ significantly in their ligand-binding profiles. (beauty104.com.tw)
  • We have developed PLA-SH2, an alternative in-solution modular domain binding assay that takes advantage of Proximity Ligation Assay and real-time PCR. (biomedcentral.com)
  • In an oligonucleotide-tagged multiplex (OTM) assay, a mixture of SH2 domains with domain-specific DNA tags are incubated with a sample spot allowing for competitive binding (single sample per well) [ 8 ]. (biomedcentral.com)
  • Structurally, PD-1 consists of extracellular immunoglobulin (Ig)-like variable domains, a transmembrane domain, and a cytoplasmic tail responsible for signal transduction and binding to scaffold molecules. (medicaltrend.org)
  • With more than 500 SH3 domains in the human genome, binding selectivity is a key issue in understanding the molecular basis of SH3 domain interactions. (ox.ac.uk)
  • The crystal structure of a complex between the C-terminal SH3 domain (SH3C) of Mona/Gads and a SLP-76 peptide has now been solved to 1.7 A. The peptide lacks the canonical SH3 domain binding motif P-x-x-P and does not form a frequently observed poly-proline type II helix. (ox.ac.uk)
  • The 3' replication has freely activated by RNase Z surface, a mature binding in receptors( reviewed in Maraia and Lamichhane 2011). (evakoch.com)
  • Endo-1,3-β-glucanase from Cellulosimicrobium cellulans is composed of a catalytic domain and a carbohydrate-binding module. (kpu-biophyschem.com)
  • SUZ RNA binding domain containi. (gsea-msigdb.org)
  • Y-box binding protein 3 [Source. (gsea-msigdb.org)
  • The residue at pY+2 does not make direct side chain interactions with the SH2 domain, but aromatic residues are not allowed. (eu.org)
  • We showed for the first time that interactions between SH2 domain probes and EGFR in cell lysate can be determined in a microliter-scale assay using SH2-PLA. (biomedcentral.com)
  • This feature along with short assay runtime makes this method a useful platform for the development of high throughput assays to determine modular domain-ligand interactions which could have wide-ranging applications in both basic and translational cancer research. (biomedcentral.com)
  • CagA can specifically bind to the SH2 domain of Src homology 2 (SH2)-containing protein tyrosine phosphatase (SHP-2), which induces spatial configuration change of SHP-2 and activates it [ 40 ]. (biomedcentral.com)
  • Non-phosphorylated peptides do not bind to the SH2 domains. (eu.org)
  • Although these factors possess remarkably similar sequence homology, they do not bind FGFRs and are involved in intracellular processes unrelated to the FGFs (Olsen et al. (beauty104.com.tw)
  • Moreover, a dominant negative form of Ras (with Ser17 substituted with Asn) blocked insulin-induced activation of ERKs in cells that overexpressed GRB2. (nih.gov)
  • Emerging evidence provided insight into the role of signal transducer and activator of transcription 3 (STAT3) in energy metabolism. (biomedcentral.com)
  • HGF forms a family with HGF-like protein (HLP), a unique protein with a domain structure similar to that of HGF ( 12 ). (spandidos-publications.com)
  • Inspection of known binders reveals that weak residues are tolerated at pY+3 when pY+1 is strong and vice-versa, but are not tolerated at both positions. (eu.org)
  • Positively charged residues are disfavoured at pY-1 and pY-2 due to the positively charged SH2 domain surface, but are tolerated when pY+1 and pY+3 are strong residues. (eu.org)
  • There are no totally invariant residues within the PH domain. (embl.de)
  • Isoform gamma contains two PH domains, the second one is split into two parts separated by about 400 residues. (embl.de)
  • As the main component, extracellular structure contains some cysteine-rich repeats domains marked as D1-D2-D3 in GFRα1-3, and D2-D3 in GFRα4 ( Figure 1 a ). (medsci.org)