• SOS1 is a guanine nucleotide exchange factor (GEF) which interacts with RAS proteins to phosphorylate GDP into GTP, or from an inactive state to an active state to signal cell proliferation. (wikipedia.org)
  • GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). (wikipedia.org)
  • Sos may act as a positive regulator of RAS by promoting guanine nucleotide exchange. (wikipedia.org)
  • A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine nucleotide exchange, Sos. (wikidata.org)
  • 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)
  • Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene. (wikipedia.org)
  • In Drosophila, the protein encoded by the 'son of sevenless' gene (Sos) contains a domain that shows sequence similarity with the catalytic domain of Cdc25. (wikipedia.org)
  • Son of sevenless (SOS) is then recruited to the plasma membrane and catalyzes the conversion of inactive Ras-GDP to active Ras-GTP that in turn recruits Raf to the plasma membrane. (springer.com)
  • Here we review new biophysical and biochemical data which provide an updated picture of the highly dynamic nanometer-sized cholesterol/sphingolipid-rich raft domains stabilised by protein-networks to form TCR signalling platforms in the T cell plasma membrane. (biomedcentral.com)
  • Early T cell signalling reactions are embedded in the complex and dynamic lipid bilayer matrix of the T cell plasma membrane and are critically defined by their lateral compartmentalisation in plasma membrane domains [ 1 , 2 ]. (biomedcentral.com)
  • We will here discuss recent data which provide a detailed picture of the membrane raft characteristics of the plasma membrane domains supporting active TCR signalling protein complexes. (biomedcentral.com)
  • Video microscopy technology resolving single molecule movement was employed to monitor the dynamic interaction of membrane-associated signalling proteins with TCR signalling clusters in plasma membrane domains. (biomedcentral.com)
  • These studies tracked the movement of Lck and LAT in the T cell plasma membrane and showed retention of these proteins in the submicron TCR signalling domains and their subsequent release. (biomedcentral.com)
  • Numerous intracellular signalling proteins interact with plasma membrane lipids of the cytoplasmic leaflet via specific lipid headgroup-binding domains. (biomedcentral.com)
  • Mouse protein citron, a putative rho/rac effector that binds to the GTP-bound forms of rho and rac. (embl.de)
  • MIM 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. (wikipedia.org)
  • After receptor activation, the alpha- and beta-gamma-subunits of G protein dissociate to activate diverse downstream pathways resulting in cellular polarization and actin reorganization. (genome.jp)
  • Ser/Thr protein kinases such as the Akt/Rac family, the beta-adrenergic receptor kinases, the mu isoform of PKC and the trypanosomal NrkA family. (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)
  • All these reports highlighted protein-protein interactions as critical driving force of TCR signalling complex formation. (biomedcentral.com)
  • Refined ensembles of solution structures have been calculated for the N-terminal SH3 domain of Grb2 (N-SH3) complexed with the ac-VPPPVPPRRR-nh2 peptide derived from residues 1135 to 1144 of the mouse SOS-1 sequence. (rcsb.org)
  • Among them are the Sprouty proteins which mainly act as inhibitors of growth factor-dependent neuronal and glial signaling pathways. (springer.com)
  • 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)
  • C. elegans protein MIG-10. (embl.de)
  • C. elegans hypothetical proteins C04D8.1, K06H7.4 and ZK632.12. (embl.de)
  • Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. (embl.de)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • Insulin Receptor Substrate 1 (IRS-1). (embl.de)
  • RTK-dependent signaling pathways provide a variety of targets for the treatment of neurological and neuropsychiatric disorders in which neurotrophins and other growth factors are released [ 8 , 9 ] (Fig. 1 ). (springer.com)
  • Biological assembly 1 assigned by authors. (rcsb.org)
  • Domain commonly found in eukaryotic signalling proteins. (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)
  • The chemokine signal is transduced by chemokine receptors (G-protein coupled receptors) expressed on the immune cells. (genome.jp)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
  • There are 196127 PH domains in 171590 proteins in SMART's nrdb database. (embl.de)
  • Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1). (embl.de)
  • Grb2 is an adaptor protein connecting the epidermal growth factor receptor and the downstream Son of sevenless 1 (SOS1), a Ras-specific guanine nucleotide exchange factor (RasGEF), which exchanges GDP by GTP. (nih.gov)
  • 2. Activation of Ras-dependent signaling pathways by G(14) -coupled receptors requires the adaptor protein TPR1. (nih.gov)
  • CRK proto-oncogene, adaptor protein [Sourc. (gsea-msigdb.org)
  • NUMB endocytic adaptor protein [Source:HGN. (gsea-msigdb.org)
  • For example, in the T cell receptor signaling system, linker for activation of T cells (LAT) phosphorylation results in the recruitment of the adaptor protein Grb2 through binding to multiple phosphorylated tyrosine sites on LAT. (elifesciences.org)
  • Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. (embl.de)
  • mitogen-activated protein kinase 3 [Source. (gsea-msigdb.org)
  • mitogen-activated protein kinase 8 [Source. (gsea-msigdb.org)
  • mitogen-activated protein kinase kinase ki. (gsea-msigdb.org)
  • The membrane receptors, adaptors, and signaling molecules form complexes to induce immediate local responses, such as actin polymerization, or transduce signals into nucleus, such as through mitogen-activated protein kinase (MAPK) signaling cascade. (elifesciences.org)
  • SOS1 is a guanine nucleotide exchange factor (GEF) which interacts with RAS proteins to phosphorylate GDP into GTP, or from an inactive state to an active state to signal cell proliferation. (wikipedia.org)
  • MIM 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. (wikipedia.org)
  • GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). (wikipedia.org)
  • Sos may act as a positive regulator of RAS by promoting guanine nucleotide exchange. (wikipedia.org)
  • 13. Requirement for Ras guanine nucleotide releasing protein 3 in coupling phospholipase C-gamma2 to Ras in B cell receptor signaling. (nih.gov)
  • In COS-1 cells, the DH domain of Sos stimulated guanine nucleotide exchange on Rac but not Cdc42 in vitro and in vivo. (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)
  • In the case of receptor tyrosine kinases (RTKs), initial receptor activation after ligand binding involves phosphorylation of specific tyrosine residues on the receptors, followed by recruitment of adaptor proteins which mediate activation of additional signaling molecules. (elifesciences.org)
  • In the tri-complex, ABI1 acted as a scaffold protein holding together SOS1 and EPS8. (biomedcentral.com)
  • 14. An activating mutation in sos-1 identifies its Dbl domain as a critical inhibitor of the epidermal growth factor receptor pathway during Caenorhabditis elegans vulval development. (nih.gov)
  • The C-terminal proline-rich (PR) domain of SOS1 regulates nSH3 open/closed conformations. (nih.gov)
  • 8. Sos1 regulates sustained TCR-mediated Erk activation. (nih.gov)
  • 16. CIIA negatively regulates the Ras-Erk1/2 signaling pathway through inhibiting the Ras-specific GEF activity of SOS1. (nih.gov)
  • 11. SOS1 over-expression in genital skin fibroblasts from hirsute women: a putative role of the SOS1/RAS pathway in the pathogenesis of hirsutism. (nih.gov)
  • 20. Type II cGMP-dependent protein kinase inhibits EGF-triggered signal transduction of the MAPK/ERK-mediated pathway in gastric cancer cells. (nih.gov)
  • Our previous study demonstrated that LPA could stimulate Rac activation, cytoskeleton reorganization, and ovarian cancer cell migration through a signaling pathway consisting of Ras-SOS1/EPS8/ABI1 tri-complex [ 14 ]. (biomedcentral.com)
  • 1. The Sos1 and Sos2 Ras-specific exchange factors: differences in placental expression and signaling properties. (nih.gov)
  • 3. Functional redundancy of Sos1 and Sos2 for lymphopoiesis and organismal homeostasis and survival. (nih.gov)
  • 5. Differential Role of the RasGEFs Sos1 and Sos2 in Mouse Skin Homeostasis and Carcinogenesis. (nih.gov)
  • Here, we develop a microfabrication strategy to produce substrates displaying mobile and immobile ligands that are separated by roughly 1 µm, and thus experience an identical cytoplasmic signaling state, enabling precision comparison of downstream signaling reactions. (elifesciences.org)
  • In 2019, the first SOS1 inhibitor, BAY-293, was published which met the quality criteria for a 'Donated Chemical Probe' as defined by the Structural Genomics Consortium. (wikipedia.org)
  • We aimed to develop inhibitory short peptides that can prevent protein interactions of SOS1/EPS8/ABI1 tri-complex, a key component essential for ovarian cancer metastasis. (biomedcentral.com)
  • Plasmids containing various regions of HA-tagged ABI1 were co-transfected into ovarian cancer cells with Flag-tagged SOS1 or Myc-tagged EPS8. (biomedcentral.com)
  • Co-immunoprecipitation and GST-pulldown assay were used to identify the regions of ABI1 responsible for SOS1 and EPS8 binding. (biomedcentral.com)
  • The blocking effects of the peptides on ABI1-SOS1 or ABI1-EPS8 interactions in vitro and in vivo were determined by GST-pulldown assay. (biomedcentral.com)
  • The formation of endogenous SOS1/EPS8/ABI1 tri-complex was detected in the event of LPA-induced ovarian cancer cell invasion. (biomedcentral.com)
  • The SH3 and poly-proline+PxxDY regions of ABI1 were responsible for SOS1 and EPS8 binding, respectively. (biomedcentral.com)
  • Inhibitory short peptides p + p-8 (ppppppppvdyedee) and SH3-3 (ekvvaiydytkdkddelsfmegaii) could block ABI1-SOS1 and ABI1-EPS8 interaction in vitro. (biomedcentral.com)
  • The integrity of SOS1/EPS8/ABI1 tri-complex may determine ovarian cancer metastatic potentials, as silencing any member of SOS1/EPS8/ABI1 tri-complex is sufficient to diminish the migration and metastatic colonization of ovarian cancer cells [ 14 ]. (biomedcentral.com)
  • These results implicate SOS1/EPS8/ABI1 tri-complex as an ideal therapeutic target, and disrupting the tri-complex may suppress the metastatic process of ovarian cancer. (biomedcentral.com)
  • In this study, we found that the SH3 and poly-proline+PxxDY regions of ABI1 are responsible for its interaction with SOS1 and EPS8, respectively. (biomedcentral.com)
  • 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)
  • This protein possesses both a domain belonging to the CDC25 family and one belonging to the CDC24 family. (embl.de)
  • The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. (embl.de)
  • this function seems to redundant with the AP-2 complex and seems to require DAB2 binding to endocytosis accessory EH domain-containing proteins such as EPS15, EPS15L1 and ITSN1. (nih.gov)
  • There are 18332 RasGEF domains in 18317 proteins in SMART's nrdb database. (embl.de)
  • Taxonomic distribution of proteins containing RasGEF domain. (embl.de)
  • The complete taxonomic breakdown of all proteins with RasGEF domain is also avaliable . (embl.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing RasGEF domain in the selected taxonomic class. (embl.de)
  • 9. Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. (nih.gov)
  • phospholipase C gamma 1 [Source:HGNC Symbo. (gsea-msigdb.org)
  • 6. A novel SOS1 mutation in Costello/CFC syndrome affects signaling in both RAS and PI3K pathways. (nih.gov)
  • Single-molecule imaging clearly resolves increased molecular binding dwell times at EphA2 clusters for both Grb2:SOS and NCK:N-WASP signaling modules. (elifesciences.org)
  • 10. The Ras-specific exchange factors mouse Sos1 (mSos1) and mSos2 are regulated differently: mSos2 contains ubiquitination signals absent in mSos1. (nih.gov)
  • Pleckstrin homology (PH) domains are small modular domains that occur in a large variety of proteins. (embl.de)
  • Pleckstrin is one of the rare proteins to contains two PH domains. (embl.de)
  • Insulin Receptor Substrate 1 (IRS-1). (embl.de)
  • GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. (embl.de)
  • Binding of GTP activates RAS proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. (wikipedia.org)
  • GEFs, GAPs, GDIs and effectors: taking a closer (3D) look at the regulation of Ras-related GTP-binding proteins. (embl.de)
  • Oxysterol binding proteins OSBP, S. cerevisiae OSH1 and YHR073w. (embl.de)
  • Several S. cerevisiae proteins involved in cell cycle regulation and bud formation like BEM2, BEM3, BUD4 and the BEM1-binding proteins BOI2 (BEB1) and BOI1 (BOB1). (embl.de)
  • Adapter protein that functions as clathrin-associated sorting protein (CLASP) required for clathrin-mediated endocytosis of selected cargo proteins. (nih.gov)