Gene Symbol: Sos
Description: SOS Ras/Rac guanine nucleotide exchange factor 1
Alias: GF1, GGF1, GINGF, HGF, NS4, SOS-1, son of sevenless homolog 1, gingival fibromatosis, hereditary, 1, guanine nucleotide exchange factor
Species: human
Products:     Sos

Top Publications

  1. Freedman T, Sondermann H, Friedland G, Kortemme T, Bar Sagi D, Marqusee S, et al. A Ras-induced conformational switch in the Ras activator Son of sevenless. Proc Natl Acad Sci U S A. 2006;103:16692-7 pubmed
    The Ras-specific guanine nucleotide-exchange factors Son of sevenless (Sos) and Ras guanine nucleotide-releasing factor 1 (RasGRF1) transduce extracellular stimuli into Ras activation by catalyzing the exchange of Ras-bound GDP for GTP...
  2. Hastings R, Newbury Ecob R, Ng A, Taylor R. A further patient with Noonan syndrome due to a SOS1 mutation and rhabdomyosarcoma. Genes Chromosomes Cancer. 2010;49:967-8 pubmed publisher
  3. Yadav K, Bar Sagi D. Allosteric gating of Son of sevenless activity by the histone domain. Proc Natl Acad Sci U S A. 2010;107:3436-40 pubmed publisher
    ..down stream of RTKs involves the stimulation of guanine nucleotide exchange by the ubiquitous guanine nucleotide exchange factor Son of sevenless (Sos)...
  4. Denayer E, Devriendt K, de Ravel T, Van Buggenhout G, Smeets E, Francois I, et al. Tumor spectrum in children with Noonan syndrome and SOS1 or RAF1 mutations. Genes Chromosomes Cancer. 2010;49:242-52 pubmed publisher
    ..One patient with a RAF1 mutation had a lesion suggestive for a giant cell tumor. This is the first report describing different tumor types in NS patients with germ line SOS1 mutations. ..
  5. Ko J, Kim J, Kim G, Yoo H. PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome. J Hum Genet. 2008;53:999-1006 pubmed publisher
    ..The molecular defects of NS are genetically heterogeneous and involve several genes other than PTPN11 related to the RAS-MAPK pathway. ..
  6. Zhao C, Du G, Skowronek K, Frohman M, Bar Sagi D. Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nat Cell Biol. 2007;9:706-12 pubmed
    The activation of Ras by the guanine nucleotide-exchange factor Son of sevenless (Sos) constitutes the rate-limiting step in the transduction process that links receptor tyrosine kinases to Ras-triggered intracellular signalling pathways...
  7. Kamioka Y, Yasuda S, Fujita Y, Aoki K, Matsuda M. Multiple decisive phosphorylation sites for the negative feedback regulation of SOS1 via ERK. J Biol Chem. 2010;285:33540-8 pubmed publisher
    ..determined parameters to study the ERK-mediated negative feedback regulation of the Ras guanine nucleotide exchange factor, son of sevenless (SOS)...
  8. Beneteau C, Cave H, Moncla A, Dorison N, Munnich A, Verloes A, et al. SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions. Eur J Hum Genet. 2009;17:1216-21 pubmed publisher
    ..The term cherubism should be used only when multiple giant cell lesions occur without any other clinical and molecular evidence of Noonan syndrome, with or without mutations of the SH3BP2 gene...
  9. Longoni M, Moncini S, Cisternino M, Morella I, Ferraiuolo S, Russo S, et al. Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations. Am J Med Genet A. 2010;152A:2176-84 pubmed publisher

More Information


  1. Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, et al. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Nature. 1993;363:85-8 pubmed
    ..Moreover, a synthetic 10-amino-acid peptide containing the sequence PPVPPR specifically blocks the interaction. These results indicate that the Grb2/hSos1 complex couples activated EGF receptor to Ras signalling. ..
  2. Hart T, Zhang Y, Gorry M, Hart P, Cooper M, Marazita M, et al. A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1. Am J Hum Genet. 2002;70:943-54 pubmed
    Hereditary gingival fibromatosis (HGF) is a rare, autosomal dominant form of gingival overgrowth. Affected individuals have a benign, slowly progressive, nonhemorrhagic, fibrous enlargement of the oral masticatory mucosa...
  3. Tartaglia M, Pennacchio L, Zhao C, Yadav K, Fodale V, Sarkozy A, et al. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Nat Genet. 2007;39:75-9 pubmed
    ..without PTPN11 or KRAS mutation have missense mutations in SOS1, which encodes a RAS-specific guanine nucleotide exchange factor. SOS1 mutations cluster at codons encoding residues implicated in the maintenance of SOS1 in its ..
  4. Feng G, Ouyang Y, Hu D, Shi Z, Gentz R, Ni J. Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway. J Biol Chem. 1996;271:12129-32 pubmed
    ..Furthermore, Grap is associated with a Ras guanine nucleotide exchange factor mSos1, primarily through its N-terminal SH3 domain...
  5. Sarkozy A, Carta C, Moretti S, Zampino G, Digilio M, Pantaleoni F, et al. Germline BRAF mutations in Noonan, LEOPARD, and cardiofaciocutaneous syndromes: molecular diversity and associated phenotypic spectrum. Hum Mutat. 2009;30:695-702 pubmed publisher
    ..Val600Glu mutant. Our findings provide evidence for a wide phenotypic diversity associated with mutations affecting BRAF, and occurrence of a clinical continuum associated with these molecular lesions. ..
  6. Margarit S, Sondermann H, Hall B, Nagar B, Hoelz A, Pirruccello M, et al. Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS. Cell. 2003;112:685-95 pubmed
    Growth factor receptors activate Ras by recruiting the nucleotide exchange factor son of sevenless (SOS) to the cell membrane, thereby triggering the production of GTP-loaded Ras...
  7. Soisson S, Nimnual A, Uy M, Bar Sagi D, Kuriyan J. Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein. Cell. 1998;95:259-68 pubmed
    ..The structure suggests that ligation of the PH domain will be coupled structurally to the GTPase binding site. ..
  8. McDonald C, Seldeen K, Deegan B, Farooq A. SH3 domains of Grb2 adaptor bind to PXpsiPXR motifs within the Sos1 nucleotide exchange factor in a discriminate manner. Biochemistry. 2009;48:4074-85 pubmed publisher
    ..Taken together, this study furthers our understanding of the assembly of a key signaling complex central to cellular machinery. ..
  9. Qian X, Vass W, Papageorge A, Anborgh P, Lowy D. N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains. Mol Cell Biol. 1998;18:771-8 pubmed
    ..functional importance of the N terminus of mouse Sos1 (mSos1), a ubiquitously expressed Ras-specific guanine nucleotide exchange factor whose C-terminal sequences bind Grb-2...
  10. Roberts A, Araki T, Swanson K, Montgomery K, Schiripo T, Joshi V, et al. Germline gain-of-function mutations in SOS1 cause Noonan syndrome. Nat Genet. 2007;39:70-4 pubmed
    ..Our results identify SOS1 mutants as a major cause of Noonan syndrome, representing the first example of activating GEF mutations associated with human disease and providing new insights into RAS-GEF regulation. ..
  11. Hanna N, Parfait B, Talaat I, Vidaud M, Elsedfy H. SOS1: a new player in the Noonan-like/multiple giant cell lesion syndrome. Clin Genet. 2009;75:568-71 pubmed publisher
    ..Gain-of-function mutations in the SOS1 gene were recently described as the second major cause of NS. Here, we report for the first time the involvement of SOS1 gene in a family with the Noonan-like/multiple giant cell lesion phenotype. ..
  12. Jang S, Lee E, Hart P, Ramaswami M, Pallos D, Hart T. Germ line gain of function with SOS1 mutation in hereditary gingival fibromatosis. J Biol Chem. 2007;282:20245-55 pubmed
    ..These findings elucidate the mechanisms for gingival overgrowth mediated by SOS1 gene mutation in humans. ..
  13. Sondermann H, Soisson S, Boykevisch S, Yang S, Bar Sagi D, Kuriyan J. Structural analysis of autoinhibition in the Ras activator Son of sevenless. Cell. 2004;119:393-405 pubmed
    The classical model for the activation of the nucleotide exchange factor Son of sevenless (SOS) involves its recruitment to the membrane, where it engages Ras...
  14. Gureasko J, Galush W, Boykevisch S, Sondermann H, Bar Sagi D, Groves J, et al. Membrane-dependent signal integration by the Ras activator Son of sevenless. Nat Struct Mol Biol. 2008;15:452-61 pubmed publisher
    The kinetics of Ras activation by Son of sevenless (SOS) changes profoundly when Ras is tethered to membranes, instead of being in solution...
  15. Zenker M, Horn D, Wieczorek D, Allanson J, Pauli S, van der Burgt I, et al. SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome. J Med Genet. 2007;44:651-6 pubmed
    ..Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been ..
  16. Swanson K, Winter J, Reis M, Bentires Alj M, Greulich H, Grewal R, et al. SOS1 mutations are rare in human malignancies: implications for Noonan Syndrome patients. Genes Chromosomes Cancer. 2008;47:253-9 pubmed
    ..Our findings suggest that SOS1 is not a significant human oncogene in most cancers. Furthermore, NS patients with SOS1 mutations may not be at increased risk of developing cancer. ..
  17. Narumi Y, Aoki Y, Niihori T, Sakurai M, Cave H, Verloes A, et al. Clinical manifestations in patients with SOS1 mutations range from Noonan syndrome to CFC syndrome. J Hum Genet. 2008;53:834-41 pubmed publisher
    ..These three patients exhibited ectodermal abnormalities, such as curly hair, sparse eyebrows, and dry skin, and two of them showed mental retardation. Our results suggest that patients with SOS1 mutations range from NS to CFC syndrome...
  18. Boriack Sjodin P, Margarit S, Bar Sagi D, Kuriyan J. The structural basis of the activation of Ras by Sos. Nature. 1998;394:337-43 pubmed
    ..structure of human H-Ras complexed with the Ras guanine-nucleotide-exchange-factor region of the Son of sevenless (Sos) protein has been determined at 2.8 A resolution...
  19. Corbalan Garcia S, Margarit S, Galron D, Yang S, Bar Sagi D. Regulation of Sos activity by intramolecular interactions. Mol Cell Biol. 1998;18:880-6 pubmed
    The guanine nucleotide exchange factor Sos mediates the coupling of receptor tyrosine kinases to Ras activation...
  20. Corbalan Garcia S, Yang S, Degenhardt K, Bar Sagi D. Identification of the mitogen-activated protein kinase phosphorylation sites on human Sos1 that regulate interaction with Grb2. Mol Cell Biol. 1996;16:5674-82 pubmed
    The Son of sevenless proteins (Sos) are guanine nucleotide exchange factors involved in the activation of Ras by cytoplasmic and receptor tyrosine kinases...
  21. Zheng J, Chen R, Corblan Garcia S, Cahill S, Bar Sagi D, Cowburn D. The solution structure of the pleckstrin homology domain of human SOS1. A possible structural role for the sequential association of diffuse B cell lymphoma and pleckstrin homology domains. J Biol Chem. 1997;272:30340-4 pubmed
  22. Gureasko J, Kuchment O, Makino D, Sondermann H, Bar Sagi D, Kuriyan J. Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless. Proc Natl Acad Sci U S A. 2010;107:3430-5 pubmed publisher
    Membrane-bound Ras is activated by translocation of the Son of Sevenless (SOS) protein to the plasma membrane...
  23. Yang S, Van Aelst L, Bar Sagi D. Differential interactions of human Sos1 and Sos2 with Grb2. J Biol Chem. 1995;270:18212-5 pubmed
    The guanine nucleotide exchange factor Son of sevenless (Sos) performs a crucial step in the coupling of receptor tyrosine kinases to Ras activation. Mammalian cells contain two related but distinct Sos proteins, Sos1 and Sos2...
  24. Houtman J, Yamaguchi H, Barda Saad M, Braiman A, Bowden B, Appella E, et al. Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1. Nat Struct Mol Biol. 2006;13:798-805 pubmed
    ..These data suggest that multipoint binding of distal adaptor proteins mediates the formation of oligomeric signaling clusters vital for intracellular signaling. ..
  25. Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, et al. EPS8 and E3B1 transduce signals from Ras to Rac. Nature. 1999;401:290-3 pubmed
    ..E3b1/Abi-1 participate in the transduction of signals from Ras to Rac, by regulating Rac-specific guanine nucleotide exchange factor (GEF) activities...
  26. Martin T, Lane J, Harrison G, Jiang W. The expression of the Nectin complex in human breast cancer and the role of Nectin-3 in the control of tight junctions during metastasis. PLoS ONE. 2013;8:e82696 pubmed publisher
    ..Nectin-3 over-expression in MDA-MB-231 cells showed reduced invasion and migration even when treated with HGF. Changes in barrier function resulted in MDAN3 cells showing less change in resistance after 2h treatment with HGF (..
  27. Akter T, Atanelishvili I, Noguchi A, Silver R, Bogatkevich G. Establishment of an indirect ELISA for detection of the novel antifibrotic peptide M10. PLoS ONE. 2017;12:e0188588 pubmed publisher
    M10 is a ten amino acid peptide generated from the intracellular cytoplasmic tail of the hepatocyte growth factor (HGF) receptor c-Met following cleavage by caspase-3...
  28. Ogaly H, Eltablawy N, El Behairy A, El Hindi H, Abd Elsalam R. Hepatocyte Growth Factor Mediates the Antifibrogenic Action of Ocimum bacilicum Essential Oil against CCl4-Induced Liver Fibrosis in Rats. Molecules. 2015;20:13518-35 pubmed publisher
    ..Expression of hepatocyte growth factor (HGF) and cytochrome P450 (CYP2EI isoform) was estimated using real-time PCR and immunohistochemistry...
  29. Konstorum A, Lowengrub J. Activation of the HGF/c-Met axis in the tumor microenvironment: A multispecies model. J Theor Biol. 2018;439:86-99 pubmed publisher
    ..Cancer-associated fibroblasts (CAFs), which reside in the tumor stroma, produce Hepatocyte Growth Factor (HGF), an important trigger for invasive and metastatic tumor behavior...
  30. Sun B, Meng X, Liu R, Yan S, Xiao Z. Mechanism study for hypoxia induced differentiation of insulin-producing cells from umbilical cord blood-derived mesenchymal stem cells. Biochem Biophys Res Commun. 2015;466:444-9 pubmed publisher
    ..improved function and viability of IPCs are the result of the interaction β cell development pathway and c-Met/HGF axis induced by hypoxia...
  31. Piao Y, Park S, Henry V, Smith B, Tiao N, Flynn D, et al. Novel MET/TIE2/VEGFR2 inhibitor altiratinib inhibits tumor growth and invasiveness in bevacizumab-resistant glioblastoma mouse models. Neuro Oncol. 2016;18:1230-41 pubmed publisher
    ..MET engagement by hepatocyte growth factor (HGF) results in receptor dimerization and autophosphorylation mediating tumor growth, invasion, and metastasis...
  32. Um J, Choii G, Park D, Kim D, Jeon S, Kang H, et al. IQ Motif and SEC7 Domain-containing Protein 3 (IQSEC3) Interacts with Gephyrin to Promote Inhibitory Synapse Formation. J Biol Chem. 2016;291:10119-30 pubmed publisher
    ..Here, we show that IQSEC3, a guanine nucleotide exchange factor for ARF6, directly interacts with gephyrin, an interaction that is critical for the inhibitory ..
  33. Yang J, Li S, Wang B, Wu Y, Chen Z, Lv M, et al. Potential biomarkers for anti-EGFR therapy in metastatic colorectal cancer. Tumour Biol. 2016;37:11645-11655 pubmed
    ..and tensin homolog (PTEN) may be potential biomarkers in the future, while activation of hepatocyte growth factor (HGF)/c-Met signaling confers resistance to anti-EGFR therapy...
  34. Du Y, Li N, Yang H, Luo C, Gong Y, Tong C, et al. Mimicking liver sinusoidal structures and functions using a 3D-configured microfluidic chip. Lab Chip. 2017;17:782-794 pubmed publisher and shear flow enhance albumin secretion independently or cooperatively, while shear flow alone enhances HGF production and CYP450 metabolism...
  35. Pandey P, Kharbanda S, Kufe D. Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein. Cancer Res. 1995;55:4000-3 pubmed
    ..The results also demonstrate that the DF3/Grb2 complex associates with the guanine nucleotide exchange protein Sos. Because Sos binds to the SH3 domains of Grb2 and, thereby, associates with Ras at the cell membrane, formation of ..
  36. Ashworth Briggs E, Toh T, Eri R, Hewitt A, Cook A. Uteroglobin and FLRG concentrations in aqueous humor are associated with age in primary open angle glaucoma patients. BMC Ophthalmol. 2018;18:57 pubmed publisher
    ..CHI3L1, FLRG, HGF, MIF, P-selectin and Uteroglobin were detected in more than 50% of samples of one or both patient groups, some of ..
  37. Matteucci E, Maroni P, Nicassio F, Ghini F, Bendinelli P, Desiderio M. Microenvironment Stimuli HGF and Hypoxia Differently Affected miR-125b and Ets-1 Function with Opposite Effects on the Invasiveness of Bone Metastatic Cells: A Comparison with Breast Carcinoma Cells. Int J Mol Sci. 2018;19: pubmed publisher
    ..i) In both the cell lines, hepatocyte growth factor (HGF) and the osteoblasts' biological products down regulated nuclear Ets-1-protein level in concomitance with ..
  38. Pinheiro D, Leirós L, Dáu J, Stumbo A, Thole A, Cortez E, et al. Cytokines, hepatic cell profiling and cell interactions during bone marrow cell therapy for liver fibrosis in cholestatic mice. PLoS ONE. 2017;12:e0187970 pubmed publisher
    ..Confocal microscopy analysis showed GFP+ BMC near regions expressing HGF and SDF-1 in the fibrotic liver...
  39. Chou Y, Chang M, Wang M, Yu F, Liu H, Harnod T, et al. PEITC inhibits human brain glioblastoma GBM 8401 cell migration and invasion through the inhibition of uPA, Rho A, and Ras with inhibition of MMP-2, -7 and -9 gene expression. Oncol Rep. 2015;34:2489-96 pubmed publisher
    ..Our findings elucidate the possible molecular mechanisms and signaling pathways of the anti-metastatic effects of PEITC on human brain glioblastoma cells, and PEITC may be considered as a therapeutic agent. ..
  40. Wang Z, Deng X, Zou W, Engelhardt J, Yan Z, Qiu J. Human Bocavirus 1 Is a Novel Helper for Adeno-associated Virus Replication. J Virol. 2017;91: pubmed publisher
    ..for the replication of the AAV2 duplex DNA genome and the production of progeny virions included the HBoV1 NP1 and NS4 proteins and a newly identified viral long noncoding RNA (BocaSR)...
  41. Munblit D, Treneva M, Peroni D, Colicino S, Chow L, Dissanayeke S, et al. Colostrum and Mature Human Milk of Women from London, Moscow, and Verona: Determinants of Immune Composition. Nutrients. 2016;8: pubmed
    ..correlation between time of milk sampling and growth factor levels in colostrum for Hepatocyte Growth Factor (HGF) and TGF?1 and TGF?3, but not TGF?2, and levels were significantly higher in colostrum than mature milk for all ..
  42. Thill R, Campbell W, Williams C. Identification and characterization of the unique guanine nucleotide exchange factor, SmgGDS, in vascular smooth muscle cells. J Cell Biochem. 2008;104:1760-70 pubmed publisher
    The guanine nucleotide exchange factor (GEF), SmgGDS, promotes nucleotide exchange by several GTPases in both the Ras and Rho families, especially by RhoA...
  43. Yamaji D, Soliman M, Kamikawa A, Ito T, Ahmed M, Okamatsu Ogura Y, et al. Species-specific control of hepatocyte growth factor expression and production in adipocytes in a differentiation-dependent manner. Domest Anim Endocrinol. 2018;62:39-48 pubmed publisher
    Hepatocyte growth factor (HGF) is a mesenchymal cell-derived factor that regulates cell growth, cell motility, and morphogenesis...
  44. Bogorad A, Lin K, Marintchev A. Novel mechanisms of eIF2B action and regulation by eIF2? phosphorylation. Nucleic Acids Res. 2017;45:11962-11979 pubmed publisher
    ..Following GTP hydrolysis, eIF2-GDP is recycled back to TC by its guanine nucleotide exchange factor (GEF), eIF2B...
  45. Patel R, Sriramoji S, Marucci M, Aziz I, Shah S, Sesti F. Cytoskeletal remodeling via Rho GTPases during oxidative and thermal stress in Caenorhabditis elegans. Biochem Biophys Res Commun. 2017;492:338-342 pubmed publisher
    ..Additionally, genetic ablation of OSG-1, a Guanine Nucleotide Exchange Factor (GEF) previously implicated in oxidative stress, was associated with constitutively lower levels of ..
  46. Pons M, Gomes C, Aguilar R, Barrios D, Aguilar Luis M, Ruiz J, et al. Immunosuppressive and angiogenic cytokine profile associated with Bartonella bacilliformis infection in post-outbreak and endemic areas of Carrion's disease in Peru. PLoS Negl Trop Dis. 2017;11:e0005684 pubmed publisher
    ..bacilliformis lysates. The presence of bacteremia was associated with low concentrations of HGF (p = 0.005), IL-15 (p = 0.002), IL-6 (p = 0.05), IP-10 (p = 0.008), MIG (p = 0.03) and MIP-1? (p = 0.03)...
  47. Guinzberg R, Díaz Cruz A, Acosta Trujillo C, Vilchis Landeros M, Vázquez Meza H, Lozano Flores C, et al. Newly synthesized cAMP is integrated at a membrane protein complex signalosome to ensure receptor response specificity. FEBS J. 2017;284:258-276 pubmed publisher
    ..Thus, each signalosome is devoted to ensure the transmission of a unique and unequivocal message through the cell. ..
  48. Madoz Gúrpide J, Zazo S, Chamizo C, Casado V, Caramés C, Gavín E, et al. Activation of MET pathway predicts poor outcome to cetuximab in patients with recurrent or metastatic head and neck cancer. J Transl Med. 2015;13:282 pubmed publisher
    ..We have investigated the impact of HGF and MET expression, MET activation (phosphorylation), MET gene status, and MET-activating mutations on cetuximab ..
  49. Marubashi S, Ohbayashi N, Fukuda M. A Varp-Binding Protein, RACK1, Regulates Dendrite Outgrowth through Stabilization of Varp Protein in Mouse Melanocytes. J Invest Dermatol. 2016;136:1672-1680 pubmed publisher a Rab32/38 effector and (ii) promotion of dendrite outgrowth by functioning as a Rab21-guanine nucleotide exchange factor. The Varp protein level has recently been shown to be negatively regulated by proteasomal ..
  50. Limpert A, Karlo J, Landreth G. Nerve growth factor stimulates the concentration of TrkA within lipid rafts and extracellular signal-regulated kinase activation through c-Cbl-associated protein. Mol Cell Biol. 2007;27:5686-98 pubmed
    ..These data provide a mechanism for the lipid raft localization of TrkA and establish the importance of the CAP adaptor protein for NGF activation of the ERKs and neuronal differentiation. ..
  51. Williams C, Harper M, Goggs R, Walsh T, Offermanns S, Poole A. Leukemia-associated Rho guanine-nucleotide exchange factor is not critical for RhoA regulation, yet is important for platelet activation and thrombosis in mice. J Thromb Haemost. 2015;13:2102-7 pubmed publisher
    ..However, although LARG may have a role in regulating the resting activation state of RhoA, its role in regulating platelet function may principally be through RhoA-independent pathways, possibly through other Rho family members. ..
  52. Ruan X, Chen T, Wang X, Li Y. Suxiao Jiuxin Pill protects cardiomyocytes against mitochondrial injury and alters gene expression during ischemic injury. Exp Ther Med. 2017;14:3523-3532 pubmed publisher
    ..3-kinase catalytic subunit ? (Pik3ca), phospholipase A2 group 4A, rap guanine nucleotide exchange factor 4 and ryanodine receptor 2 were detected using reverse transcription-quantitative polymerase chain ..
  53. Howes J, Akan D, Burns M, Rossanese O, Waterson A, Fesik S. Small Molecule-Mediated Activation of RAS Elicits Biphasic Modulation of Phospho-ERK Levels that Are Regulated through Negative Feedback on SOS1. Mol Cancer Ther. 2018;17:1051-1060 pubmed publisher
    ..Our laboratory has recently discovered small molecules that activate Son of Sevenless (SOS)-catalyzed nucleotide exchange on RAS and inhibit downstream signaling...
  54. Sakamoto A, Matsuda T, Kawaguchi K, Takaoka A, Maruyama M. Involvement of Zizimin2/3 in the age-related defect of peritoneal B-1a cells as a source of anti-bacterial IgM. Int Immunol. 2017;29:431-438 pubmed publisher
    Zizimin2 (Ziz2), also known as dedicator of cytokinesis 11 (DOCK11), is a guanine nucleotide exchange factor that is predominantly expressed in lymphoid tissues...
  55. Zhu T, He H, Kole S, D Souza T, Agarwal R, Morin P, et al. Filamin A-mediated down-regulation of the exchange factor Ras-GRF1 correlates with decreased matrix metalloproteinase-9 expression in human melanoma cells. J Biol Chem. 2007;282:14816-26 pubmed
    ..indicated that this phenomenon was associated with destabilization and ubiquitylation of Ras-GRF1, a guanine nucleotide exchange factor that activates H-Ras by facilitating the release of GDP...
  56. Li C, Luo X, Zhao S, Siu G, Liang Y, Chan H, et al. COPI-TRAPPII activates Rab18 and regulates its lipid droplet association. EMBO J. 2017;36:441-457 pubmed publisher
    ..protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1...
  57. Sugiyama K, Tago K, Matsushita S, Nishikawa M, Sato K, Muto Y, et al. Heterotrimeric G protein G?s subunit attenuates PLEKHG2, a Rho family-specific guanine nucleotide exchange factor, by direct interaction. Cell Signal. 2017;32:115-123 pubmed publisher
    PLEKHG2 is a G??-dependent guanine nucleotide exchange factor (GEF) for the small GTPases Rac and Cdc42, and has been shown to mediate signalling pathways such as actin cytoskeleton reorganization and serum response element (SRE)-..
  58. D Angelo G, Martini J, Iiri T, Fantl W, Martial J, Weiner R. 16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells. Mol Endocrinol. 1999;13:692-704 pubmed
    ..In contrast, 16K hPRL prevented the VEGF-induced phosphorylation and dissociation of Sos from Grb2 at 5 min, consistent with inhibition by 16K hPRL of the MEK/MAPK feedback on Sos...
  59. Siddiqui Jain A, Hoj J, Hargiss J, Hoj T, Payne C, Ritchie C, et al. Pyridine-pyrimidine amides that prevent HGF-induced epithelial scattering by two distinct mechanisms. Bioorg Med Chem Lett. 2017;27:3992-4000 pubmed publisher
    Stimulation of cultured epithelial cells with scatter factor/hepatocyte growth factor (HGF) results in individual cells detaching and assuming a migratory and invasive phenotype...
  60. Chen J, Han S, Zou X, Zou Y. [Association between hepatocyte growth factor in tears and corneal haze in rabbits early after epipolis laser in situ keratomileusis]. Nan Fang Yi Ke Da Xue Xue Bao. 2017;37:1551-1554 pubmed
    To study the dynamic changes of levels of hepatocyte growth factor (HGF) in tears and their association with corneal haze in rabbits early after epipolis laser in situ keratomileusis (Epi-LASIK)...
  61. Yang Z, Barnes C, Kumar R. Human epidermal growth factor receptor 2 status modulates subcellular localization of and interaction with estrogen receptor alpha in breast cancer cells. Clin Cancer Res. 2004;10:3621-8 pubmed
    ..In addition, HER2 up-regulation resulted in ER interaction with Sos, a component of Ras signaling, and hyperstimulation of the mitogen-activated protein kinase extracellular signal-..
  62. Zarich N, Oliva J, Martinez N, Jorge R, Ballester A, Gutiérrez Eisman S, et al. Grb2 is a negative modulator of the intrinsic Ras-GEF activity of hSos1. Mol Biol Cell. 2006;17:3591-7 pubmed
  63. Sadoshima J, Izumo S. The heterotrimeric G q protein-coupled angiotensin II receptor activates p21 ras via the tyrosine kinase-Shc-Grb2-Sos pathway in cardiac myocytes. EMBO J. 1996;15:775-87 pubmed
    ..Ang II causes rapid tyrosine phosphorylation of Shc and its association with Grb2 and mSos-1, a guanine nucleotide exchange factor of p21 ras. This leads to translocation of mSos-1 to the membrane fraction...
  64. Kandalam S, Sindji L, Delcroix G, Violet F, Garric X, André E, et al. Pharmacologically active microcarriers delivering BDNF within a hydrogel: Novel strategy for human bone marrow-derived stem cells neural/neuronal differentiation guidance and therapeutic secretome enhancement. Acta Biomater. 2017;49:167-180 pubmed publisher
    ..Moreover, the 3D environment (PAMs or hydrogel) increased MIAMI cells secretion of growth factors (b-NGF, SCF, HGF, LIF, PlGF-1, SDF-1α, VEGF-A & D) and chemokines (MIP-1α & β, RANTES, IL-8)...
  65. Liu Z, Nickel C, Cantley L. HGF promotes adhesion of ATP-depleted renal tubular epithelial cells in a MAPK-dependent manner. Am J Physiol Renal Physiol. 2001;281:F62-70 pubmed
    Hepatocyte growth factor (HGF) has been shown to enhance recovery from renal tubular ischemia. We investigated the possibility that HGF improves recovery by preventing ischemia-induced loss of cell adhesion...
  66. Lin X, Gu Y, Kapoor A, Wei F, Aziz T, Ojo D, et al. Overexpression of MUC1 and Genomic Alterations in Its Network Associate with Prostate Cancer Progression. Neoplasia. 2017;19:857-867 pubmed publisher
    ..0458) and DFS (P=.0163) in melanoma patients (n=367). MUC1 upregulation is associated with CRPC and bone metastasis. A nine-gene signature derived from a MUC1 network predicts PC recurrence. ..
  67. Sacco E, Metalli D, Busti S, Fantinato S, D Urzo A, Mapelli V, et al. Catalytic competence of the Ras-GEF domain of hSos1 requires intra-REM domain interactions mediated by phenylalanine 577. FEBS Lett. 2006;580:6322-8 pubmed
    ..We show that an intra-REM domain interaction, mediated by phenylalanine 577, is required to allow interaction of the REM domain with the catalytic core, constraining it in the active conformation. ..
  68. Kong S, Aoki A, Iwasaki K, Mizutani K, Katagiri S, Suda T, et al. Biological effects of Er:YAG laser irradiation on the proliferation of primary human gingival fibroblasts. J Biophotonics. 2017;: pubmed publisher
    ..Thus, despite causing transient cellular damage, Er:YAG laser irradiation at 6.3?J cm-2 strongly potentiated HGF proliferation via photo-thermal stress, suggesting potential wound-healing benefit.
  69. Chen W, Yan Y, Song C, Ding Y, Du T. Microvesicles derived from human Wharton's Jelly mesenchymal stem cells ameliorate ischemia-reperfusion-induced renal fibrosis by releasing from G2/M cell cycle arrest. Biochem J. 2017;474:4207-4218 pubmed publisher
    ..into rats immediately after ischemia of the left kidney, and Erk1/2 activator hepatocyte growth factor (HGF) or inhibitor U0126 was administrated...
  70. Heldin J, O Callaghan P, Hernández Vera R, Fuchs P, Gerwins P, Kreuger J. FGD5 sustains vascular endothelial growth factor A (VEGFA) signaling through inhibition of proteasome-mediated VEGF receptor 2 degradation. Cell Signal. 2017;40:125-132 pubmed publisher
    The complete repertoire of endothelial functions elicited by FGD5, a guanine nucleotide exchange factor activating the Rho GTPase Cdc42, has yet to be elucidated...
  71. Qin Z, Worthen C, Quan T. Cell-size-dependent upregulation of HGF expression in dermal fibroblasts: Impact on human skin connective tissue aging. J Dermatol Sci. 2017;88:289-297 pubmed publisher
    ..Hepatocyte growth factor (HGF) acts as an anti-fibrotic factor by suppression of collagen production...
  72. Kon Kozlowski M, Pani G, Pawson T, Siminovitch K. The tyrosine phosphatase PTP1C associates with Vav, Grb2, and mSos1 in hematopoietic cells. J Biol Chem. 1996;271:3856-62 pubmed
    ..the possibility that this enzyme interacts with the product of the Vav proto-oncogene, a putative guanine nucleotide exchange factor expressed exclusively in hemopoietic cells...
  73. Hossain M, Das U, Umemura N, Sakagami H, Balzarini J, De Clercq E, et al. Tumour-specific cytotoxicity and structure-activity relationships of novel 1-[3-(2-methoxyethylthio)propionyl]-3,5-bis(benzylidene)-4-piperidones. Bioorg Med Chem. 2016;24:2206-14 pubmed publisher
    ..Evaluation of these compounds against non-malignant HGF and HPLF cells revealed the tumour-specific toxicity...
  74. Hadziselimovic N, De Geyter C, Demougin P, Oakeley E, Hadziselimovic F. Decreased expression of FGFR1, SOS1, RAF1 genes in cryptorchidism. Urol Int. 2010;84:353-61 pubmed publisher
    ..Based on our results, it is possible that a subtle dysfunction (expression) of the FGFR1, SOS1 and RAF1 genes is involved in the development of the most common male reproductive tract disorder - unilateral or bilateral cryptorchidism. ..
  75. Pettit A, Jonsson W, Bargoud A, Mirek E, Peelor F, Wang Y, et al. Dietary Methionine Restriction Regulates Liver Protein Synthesis and Gene Expression Independently of Eukaryotic Initiation Factor 2 Phosphorylation in Mice. J Nutr. 2017;147:1031-1040 pubmed publisher
    ..Ala enrichment with deuterium was measured to calculate protein synthesis rates. The guanine nucleotide exchange factor activity of eIF2B was measured alongside p-eIF2 and hepatic mRNA expression levels at 2 d and 5 wk...
  76. Zhilai Z, Biling M, Sujun Q, Chao D, Benchao S, Shuai H, et al. Preconditioning in lowered oxygen enhances the therapeutic potential of human umbilical mesenchymal stem cells in a rat model of spinal cord injury. Brain Res. 2016;1642:426-435 pubmed publisher
    ..while physioxia up-regulated the expression of trophic and growth factors, including hepatocyte growth factor (HGF), brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor(VEGF), in UCMSCs...
  77. Tafazoli A, Eshraghi P, Pantaleoni F, Vakili R, Moghaddassian M, Ghahraman M, et al. Novel mutations and their genotype-phenotype correlations in patients with Noonan syndrome, using next-generation sequencing. Adv Med Sci. 2018;63:87-93 pubmed publisher
    ..Obviously, more comprehensive and new technologies like NGS methods are the best choice for detection of molecular defects in patients for genotype, phenotype correlation and disease management. ..
  78. Aliebrahimi S, Montasser Kouhsari S, Ostad S, Arab S, Karami L. Identification of Phytochemicals Targeting c-Met Kinase Domain using Consensus Docking and Molecular Dynamics Simulation Studies. Cell Biochem Biophys. 2018;76:135-145 pubmed publisher
    ..Considering the pivotal role of HGF/c-Met signaling in carcinogenesis, our results propose ZINC08234189 and ZINC03871891 as the therapeutic options to ..
  79. Ritt D, Abreu Blanco M, Bindu L, Durrant D, Zhou M, Specht S, et al. Inhibition of Ras/Raf/MEK/ERK Pathway Signaling by a Stress-Induced Phospho-Regulatory Circuit. Mol Cell. 2016;64:875-887 pubmed publisher
  80. Wong A, Lamothe B, Lee A, Schlessinger J, Lax I, Li A. FRS2 alpha attenuates FGF receptor signaling by Grb2-mediated recruitment of the ubiquitin ligase Cbl. Proc Natl Acad Sci U S A. 2002;99:6684-9 pubmed
    ..These observations highlight the importance of FRS2 alpha in the assembly of both positive (i.e., Sos, phosphatidylinositol 3-kinase) and negative (i.e...
  81. Lo C, Lo J, Sato P, Yeung T, Mok S, Yip K. Monitoring of ovarian cancer cell invasion in real time with frequency-dependent impedance measurement. Am J Physiol Cell Physiol. 2016;311:C1040-C1047 pubmed publisher
    ..The invasion was augmented in the presence of hepatocyte growth factor (HGF). The enhancing effect of HGF was attenuated by c-Met inhibitor (SU11274)...