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Gene Review

SOS1  -  son of sevenless homolog 1 (Drosophila)

Homo sapiens

Synonyms: GF1, GGF1, GINGF, HGF, NS4, ...
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Disease relevance of SOS1


Psychiatry related information on SOS1


High impact information on SOS1

  • Here, we report that 22 of 129 individuals with Noonan syndrome without PTPN11 or KRAS mutation have missense mutations in SOS1, which encodes a RAS-specific guanine nucleotide exchange factor [1].
  • The phenotype associated with SOS1 defects lies within the Noonan syndrome spectrum but is distinctive, with a high prevalence of ectodermal abnormalities but generally normal development and linear growth [1].
  • Eps8 is a substrate of the EGFR, which is held in a complex with Sos1 by the adaptor protein E3bl (ref. 2), thereby mediating activation of Rac [7].
  • Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 [8].
  • {beta}4 integrin activates a Shp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth [9].

Chemical compound and disease context of SOS1


Biological context of SOS1

  • The SH3 domains of Grb2 form a stable complex with SOS1 and two proteins of 75 kD and 120 kD, which undergo tyrosine phosphorylation in Fc gamma RIIA stimulated cells [12].
  • The SOS3-SOS2 kinase complex regulates the expression and activity of ion transporters such as SOS1 to re-establish cellular ionic homeostasis under salinity [13].
  • An autosomal dominant form of hereditary gingival fibromatosis (HGF, MIM 135300) was recently mapped to chromosome 2p21 in a large Brazilian family and there was an earlier report of GF in a boy with a cytogenetic duplication involving 2p13-->p21 [14].
  • Molecular cytogenetic analysis of the 2p13-->p21 duplication associated with GF showed that the duplicated region was proximal to the candidate interval for HGF [14].
  • To test evidence of increased cell proliferation, we studied histological, morphological, and proliferation characteristics in monolayer and three-dimensional cultures of fibroblasts with the SOS1 g.126,142-126,143insC mutation [15].

Anatomical context of SOS1

  • The protein kinase complex then phosphorylates and activates various ion transporters, such as the plasma membrane Na(+)/H(+) antiporter SOS1 [16].
  • Expression of alternative forms of Ras exchange factors GRF and SOS1 in different human tissues and cell lines [17].
  • Stimulation of Jurkat cells with either anti-TCR beta or anti-CD3 monoclonal antibody failed to induce substantial tyrosine phosphorylation of Shc proteins or their association with Grb2 which forms a complex with the guanine nucleotide exchange factor hSOS [18].
  • To demonstrate the practical potential and limitations of global analyses of ITC titrations for the study of cooperative multiprotein interactions, we have examined the interactions of three proteins that are critical for signal transduction after T-cell activation, LAT, Grb2, and Sos1 [19].
  • Hepatocyte growth factor-scatter factor (HGF-SF) is a pleiotropic protein implicated in tumor formation and metastasis [4].

Associations of SOS1 with chemical compounds


Physical interactions of SOS1

  • This insertion mutation, which segregates in a dominant manner over four generations, introduces a frameshift and creates a premature stop codon, abolishing four functionally important proline-rich SH3 binding domains normally present in the carboxyl-terminal region of the SOS1 protein [2].
  • The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for activation of the mitogen-activated protein kinase cascade in a B-cell line [23].

Regulatory relationships of SOS1


Other interactions of SOS1

  • Mammalian cells contain two related but distinct Sos proteins, Sos1 and Sos2 [25].
  • The expression of p21Ras and its regulatory proteins; hSOS1 and p120GAP were studied [26].
  • Insulin-dependent translocation of Shc, SOS1, and MAPK to lipid raft microdomains was markedly attenuated by FLNa expression [27].
  • Although the mechanisms of Ras GEF regulation are unclear, recent studies suggest that translocation of SOS1 to the plasma membrane, where Ras is located, might be responsible for Ras activation [28].
  • Decreased expression of the p21ras stimulatory factor hSOS in PBMC from inactive SLE patients [29].

Analytical, diagnostic and therapeutic context of SOS1


  1. Gain-of-function SOS1 mutations cause a distinctive form of Noonan syndrome. Tartaglia, M., Pennacchio, L.A., Zhao, C., Yadav, K.K., Fodale, V., Sarkozy, A., Pandit, B., Oishi, K., Martinelli, S., Schackwitz, W., Ustaszewska, A., Martin, J., Bristow, J., Carta, C., Lepri, F., Neri, C., Vasta, I., Gibson, K., Curry, C.J., Siguero, J.P., Digilio, M.C., Zampino, G., Dallapiccola, B., Bar-Sagi, D., Gelb, B.D. Nat. Genet. (2007) [Pubmed]
  2. A mutation in the SOS1 gene causes hereditary gingival fibromatosis type 1. Hart, T.C., Zhang, Y., Gorry, M.C., Hart, P.S., Cooper, M., Marazita, M.L., Marks, J.M., Cortelli, J.R., Pallos, D. Am. J. Hum. Genet. (2002) [Pubmed]
  3. 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. Zheng, J., Chen, R.H., Corblan-Garcia, S., Cahill, S.M., Bar-Sagi, D., Cowburn, D. J. Biol. Chem. (1997) [Pubmed]
  4. Tumor HGF lacks prognostic significance in Mexican breast cancer patients. Pruefer, F.G., Unger-Salda??a, K., Mohamier, L., Ram??rez, M., Su??rez, J., Ramirez, M.T., Maldonado, V., Mel??ndez-Zajgla, J. J. Exp. Clin. Cancer Res. (2006) [Pubmed]
  5. Germ line gain of function with SOS1 mutation in hereditary gingival fibromatosis. Jang, S.I., Lee, E.J., Hart, P.S., Ramaswami, M., Pallos, D., Hart, T.C. J. Biol. Chem. (2007) [Pubmed]
  6. Signal transduction abnormalities in Alzheimer's disease: evidence of a pathogenic stimuli. McShea, A., Zelasko, D.A., Gerst, J.L., Smith, M.A. Brain Res. (1999) [Pubmed]
  7. The Eps8 protein coordinates EGF receptor signalling through Rac and trafficking through Rab5. Lanzetti, L., Rybin, V., Malabarba, M.G., Christoforidis, S., Scita, G., Zerial, M., Di Fiore, P.P. Nature (2000) [Pubmed]
  8. Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2. Chardin, P., Camonis, J.H., Gale, N.W., van Aelst, L., Schlessinger, J., Wigler, M.H., Bar-Sagi, D. Science (1993) [Pubmed]
  9. {beta}4 integrin activates a Shp2-Src signaling pathway that sustains HGF-induced anchorage-independent growth. Bertotti, A., Comoglio, P.M., Trusolino, L. J. Cell Biol. (2006) [Pubmed]
  10. Chronic exposure to fulvestrant promotes overexpression of the c-Met receptor in breast cancer cells: implications for tumour-stroma interactions. Hiscox, S., Jordan, N.J., Jiang, W., Harper, M., McClelland, R., Smith, C., Nicholson, R.I. Endocr. Relat. Cancer (2006) [Pubmed]
  11. Localization, genomic organization, and alternative transcription of a novel human SAM-dependent methyltransferase gene on chromosome 2p22-->p21. Zhang, Y., Gorry, M.C., Hart, P.S., Pettenati, M.J., Wang, L., Marks, J.J., Lu, X., Hart, T.C. Cytogenet. Cell Genet. (2001) [Pubmed]
  12. Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking. Robinson, A., Gibbins, J., Rodríguez-Liñares, B., Finan, P.M., Wilson, L., Kellie, S., Findell, P., Watson, S.P. Blood (1996) [Pubmed]
  13. Molecular genetic perspectives on cross-talk and specificity in abiotic stress signalling in plants. Chinnusamy, V., Schumaker, K., Zhu, J.K. J. Exp. Bot. (2004) [Pubmed]
  14. Genetic heterogeneity of gingival fibromatosis on chromosome 2p. Shashi, V., Pallos, D., Pettenati, M.J., Cortelli, J.R., Fryns, J.P., von Kap-Herr, C., Hart, T.C. J. Med. Genet. (1999) [Pubmed]
  15. Characterization of fibroblasts with son of sevenless-1 mutation. Lee, E.J., Jang, S.I., Pallos, D., Kather, J., Hart, T.C. J. Dent. Res. (2006) [Pubmed]
  16. Regulation of ion homeostasis under salt stress. Zhu, J.K. Curr. Opin. Plant Biol. (2003) [Pubmed]
  17. Expression of alternative forms of Ras exchange factors GRF and SOS1 in different human tissues and cell lines. Guerrero, C., Rojas, J.M., Chedid, M., Esteban, L.M., Zimonjic, D.B., Popescu, N.C., Font de Mora, J., Santos, E. Oncogene (1996) [Pubmed]
  18. The T-cell antigen receptor utilizes Lck, Raf-1, and MEK-1 for activating mitogen-activated protein kinase. Evidence for the existence of a second protein kinase C-dependent pathway in an Lck-negative Jurkat cell mutant. Gupta, S., Weiss, A., Kumar, G., Wang, S., Nel, A. J. Biol. Chem. (1994) [Pubmed]
  19. Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: Application to adaptor protein complexes in cell signaling. Houtman, J.C., Brown, P.H., Bowden, B., Yamaguchi, H., Appella, E., Samelson, L.E., Schuck, P. Protein Sci. (2007) [Pubmed]
  20. New approach to cancer therapy: the application of signal transduction to anti-cancer drug. Osada, S., Saji, S. Current medicinal chemistry. Anti-cancer agents. (2003) [Pubmed]
  21. Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1. Kim, M.J., Chang, J.S., Park, S.K., Hwang, J.I., Ryu, S.H., Suh, P.G. Biochemistry (2000) [Pubmed]
  22. The two SH2-domain-containing inositol 5-phosphatases SHIP1 and SHIP2 are coexpressed in human T lymphocytes. Bruyns, C., Pesesse, X., Moreau, C., Blero, D., Erneux, C. Biol. Chem. (1999) [Pubmed]
  23. The membrane immunoglobulin receptor utilizes a Shc/Grb2/hSOS complex for activation of the mitogen-activated protein kinase cascade in a B-cell line. Kumar, G., Wang, S., Gupta, S., Nel, A. Biochem. J. (1995) [Pubmed]
  24. Identification of the mitogen-activated protein kinase phosphorylation sites on human Sos1 that regulate interaction with Grb2. Corbalan-Garcia, S., Yang, S.S., Degenhardt, K.R., Bar-Sagi, D. Mol. Cell. Biol. (1996) [Pubmed]
  25. Differential interactions of human Sos1 and Sos2 with Grb2. Yang, S.S., Van Aelst, L., Bar-Sagi, D. J. Biol. Chem. (1995) [Pubmed]
  26. Normal p21Ras/MAP kinase pathway expression and function in PBMC from patients with polycystic ovary disease. Buchs, A., Chagag, P., Weiss, M., Kish, E., Levinson, R., Aharoni, D., Rapoport, M.J. Int. J. Mol. Med. (2004) [Pubmed]
  27. Interaction of filamin A with the insulin receptor alters insulin-dependent activation of the mitogen-activated protein kinase pathway. He, H.J., Kole, S., Kwon, Y.K., Crow, M.T., Bernier, M. J. Biol. Chem. (2003) [Pubmed]
  28. Guanine nucleotide exchange factors: activators of Ras superfamily proteins. Overbeck, A.F., Brtva, T.R., Cox, A.D., Graham, S.M., Huff, S.Y., Khosravi-Far, R., Quilliam, L.A., Solski, P.A., Der, C.J. Mol. Reprod. Dev. (1995) [Pubmed]
  29. Decreased expression of the p21ras stimulatory factor hSOS in PBMC from inactive SLE patients. Rapoport, M.J., Mor, A., Amit, M., Rosenberg, R., Ramot, Y., Mizrachi, A., Wysenbeek, A.J. Lupus (1999) [Pubmed]
  30. Isolated Sos1 PH domain exhibits germinal vesicle breakdown-inducing activity in Xenopus oocytes. Font de Mora, J., Guerrero, C., Mahadevan, D., Coque, J.J., Rojas, J.M., Esteban, L.M., Rebecchi, M., Santos, E. J. Biol. Chem. (1996) [Pubmed]
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