RAS genes (e.g., MIM 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of signals that control cell growth and differentiation. Binding of GTP activates RAS proteins, and subsequent hydrolysis of the bound GTP to GDP and phosphate inactivates signaling by these proteins. GTP binding can be catalyzed by guanine nucleotide exchange factors for RAS, and GTP hydrolysis can be accelerated by GTPase-activating proteins (GAPs). The first exchange factor to be identified for RAS was the S. cerevisiae CDC25 gene product. Genetic analysis indicated that CDC25 is essential for activation of RAS proteins. 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. Sos may act as a positive regulator of RAS by promoting guanine nucleotide exchange.[supplied by OMIM][3]
Clinical significance
Recent studies also show that mutations in Sos1 can cause Noonan syndrome[4] and hereditary gingival fibromatosis type 1.[5] Noonan syndrome has also been shown to be caused by mutations in KRAS and PTPN11 genes.[6] activators of the MAP kinase pathway.
↑Webb GC, Jenkins NA, Largaespada DA, Copeland NG, Fernandez CS, Bowtell DD (February 1994). "Mammalian homologues of the Drosophila Son of sevenless gene map to murine chromosomes 17 and 12 and to human chromosomes 2 and 14, respectively". Genomics. 18 (1): 14–9. doi:10.1006/geno.1993.1421. PMID8276400.
↑Xiao S, Wang X, Qu B, Yang M, Liu G, Bu L, Wang Y, Zhu L, Lei H, Hu L, Zhang X, Liu J, Zhao G, Kong X (November 2000). "Refinement of the locus for autosomal dominant hereditary gingival fibromatosis (GINGF) to a 3.8-cM region on 2p21". Genomics. 68 (3): 247–52. doi:10.1006/geno.2000.6285. PMID10995566.
↑Tartaglia M, Mehler EL, Goldberg R, Zampino G, Brunner HG, Kremer H, van der Burgt I, Crosby AH, Ion A, Jeffery S, Kalidas K, Patton MA, Kucherlapati RS, Gelb BD (December 2001). "Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome". Nat. Genet. 29 (4): 465–8. doi:10.1038/ng772. PMID11704759.
↑ 7.07.1Scita G, Nordstrom J, Carbone R, Tenca P, Giardina G, Gutkind S, Bjarnegård M, Betsholtz C, Di Fiore PP (September 1999). "EPS8 and E3B1 transduce signals from Ras to Rac". Nature. 401 (6750): 290–3. doi:10.1038/45822. PMID10499589.
↑ 10.010.110.2Okada S, Pessin JE (October 1996). "Interactions between Src homology (SH) 2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor". J. Biol. Chem. 271 (41): 25533–8. doi:10.1074/jbc.271.41.25533. PMID8810325.
↑ 12.012.1Buday L, Egan SE, Rodriguez Viciana P, Cantrell DA, Downward J (March 1994). "A complex of Grb2 adaptor protein, Sos exchange factor, and a 36-kDa membrane-bound tyrosine phosphoprotein is implicated in ras activation in T cells". J. Biol. Chem. 269 (12): 9019–23. PMID7510700.
↑ 16.016.1Foehr ED, Tatavos A, Tanabe E, Raffioni S, Goetz S, Dimarco E, De Luca M, Bradshaw RA (May 2000). "Discoidin domain receptor 1 (DDR1) signaling in PC12 cells: activation of juxtamembrane domains in PDGFR/DDR/TrkA chimeric receptors". FASEB J. 14 (7): 973–81. PMID10783152.
↑Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, Schlessinger J (May 1997). "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell. 89 (5): 693–702. doi:10.1016/s0092-8674(00)80252-4. PMID9182757.
↑ 18.018.118.2Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O (October 1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochem. Biophys. Res. Commun. 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. PMID9344843.
↑ 19.019.1Pandey P, Kharbanda S, Kufe D (September 1995). "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein". Cancer Res. 55 (18): 4000–3. PMID7664271.
↑Blagoev B, Kratchmarova I, Ong SE, Nielsen M, Foster LJ, Mann M (March 2003). "A proteomics strategy to elucidate functional protein-protein interactions applied to EGF signaling". Nat. Biotechnol. 21 (3): 315–8. doi:10.1038/nbt790. PMID12577067.
↑Liu SK, McGlade CJ (Dec 1998). "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine-phosphorylated Shc". Oncogene. 17 (24): 3073–82. doi:10.1038/sj.onc.1202337. PMID9872323.
↑Robinson A, Gibbins J, Rodríguez-Liñares B, Finan PM, Wilson L, Kellie S, Findell P, Watson SP (July 1996). "Characterization of Grb2-binding proteins in human platelets activated by Fc gamma RIIA cross-linking". Blood. 88 (2): 522–30. PMID8695800.
↑Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B, Schlessinger J (May 1993). "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature. 363 (6424): 85–8. doi:10.1038/363085a0. PMID8479541.
↑Reif K, Buday L, Downward J, Cantrell DA (May 1994). "SH3 domains of the adapter molecule Grb2 complex with two proteins in T cells: the guanine nucleotide exchange protein Sos and a 75-kDa protein that is a substrate for T cell antigen receptor-activated tyrosine kinases". J. Biol. Chem. 269 (19): 14081–7. PMID8188688.
↑D'Angelo G, Martini JF, Iiri T, Fantl WJ, Martial J, Weiner RI (May 1999). "16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells". Mol. Endocrinol. 13 (5): 692–704. doi:10.1210/mend.13.5.0280. PMID10319320.
↑Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB (August 1995). "Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR". J. Biol. Chem. 270 (31): 18428–36. doi:10.1074/jbc.270.31.18428. PMID7629168.
↑Park RK, Izadi KD, Deo YM, Durden DL (September 1999). "Role of Src in the modulation of multiple adaptor proteins in FcalphaRI oxidant signaling". Blood. 94 (6): 2112–20. PMID10477741.
↑ 31.031.1Park RK, Erdreich-Epstein A, Liu M, Izadi KD, Durden DL (Dec 1999). "High affinity IgG receptor activation of Src family kinases is required for modulation of the Shc-Grb2-Sos complex and the downstream activation of the nicotinamide adenine dinucleotide phosphate (reduced) oxidase". J. Immunol. 163 (11): 6023–34. PMID10570290.
↑Spivak-Kroizman T, Mohammadi M, Hu P, Jaye M, Schlessinger J, Lax I (May 1994). "Point mutation in the fibroblast growth factor receptor eliminates phosphatidylinositol hydrolysis without affecting neuronal differentiation of PC12 cells". J. Biol. Chem. 269 (20): 14419–23. PMID7514169.
↑Margarit SM, Sondermann H, Hall BE, Nagar B, Hoelz A, Pirruccello M, Bar-Sagi D, Kuriyan J (March 2003). "Structural evidence for feedback activation by Ras.GTP of the Ras-specific nucleotide exchange factor SOS". Cell. 112 (5): 685–95. doi:10.1016/s0092-8674(03)00149-1. PMID12628188.
↑Boriack-Sjodin PA, Margarit SM, Bar-Sagi D, Kuriyan J (July 1998). "The structural basis of the activation of Ras by Sos". Nature. 394 (6691): 337–43. doi:10.1038/28548. PMID9690470.
↑Schroeder JA, Thompson MC, Gardner MM, Gendler SJ (April 2001). "Transgenic MUC1 interacts with epidermal growth factor receptor and correlates with mitogen-activated protein kinase activation in the mouse mammary gland". J. Biol. Chem. 276 (16): 13057–64. doi:10.1074/jbc.M011248200. PMID11278868.
↑Wunderlich L, Faragó A, Buday L (January 1999). "Characterization of interactions of Nck with Sos and dynamin". Cell. Signal. 11 (1): 25–9. doi:10.1016/s0898-6568(98)00027-8. PMID10206341.
↑Braverman LE, Quilliam LA (February 1999). "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing adapter protein having similar binding and biological properties to Nck". J. Biol. Chem. 274 (9): 5542–9. doi:10.1074/jbc.274.9.5542. PMID10026169.
↑Kim MJ, Chang JS, Park SK, Hwang JI, Ryu SH, Suh PG (July 2000). "Direct interaction of SOS1 Ras exchange protein with the SH3 domain of phospholipase C-gamma1". Biochemistry. 39 (29): 8674–82. doi:10.1021/bi992558t. PMID10913276.
↑Scholler JK, Perez-Villar JJ, O'Day K, Kanner SB (August 2000). "Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of phospholipase Cgamma1". Eur. J. Immunol. 30 (8): 2378–87. doi:10.1002/1521-4141(2000)30:8<2378::AID-IMMU2378>3.0.CO;2-E. PMID10940929.
↑Watanabe S, Take H, Takeda K, Yu ZX, Iwata N, Kajigaya S (November 2000). "Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes". Biochem. Biophys. Res. Commun. 278 (1): 167–74. doi:10.1006/bbrc.2000.3760. PMID11071869.
Nel AE, Gupta S, Lee L, Ledbetter JA, Kanner SB (1995). "Ligation of the T-cell antigen receptor (TCR) induces association of hSos1, ZAP-70, phospholipase C-gamma 1, and other phosphoproteins with Grb2 and the zeta-chain of the TCR". J. Biol. Chem. 270 (31): 18428–36. doi:10.1074/jbc.270.31.18428. PMID7629168.
Pandey P, Kharbanda S, Kufe D (1995). "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein". Cancer Res. 55 (18): 4000–3. PMID7664271.
Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, Bar-Sagi D, Margolis B, Schlessinger J (1993). "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature. 363 (6424): 85–8. doi:10.1038/363085a0. PMID8479541.
Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, Bar-Sagi D (1993). "Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2". Science. 260 (5112): 1338–43. doi:10.1126/science.8493579. PMID8493579.
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 kinases to the Ras pathway". J. Biol. Chem. 271 (21): 12129–32. doi:10.1074/jbc.271.21.12129. PMID8647802.
Okada S, Pessin JE (1996). "Interactions between Src homology (SH) 2/SH3 adapter proteins and the guanylnucleotide exchange factor SOS are differentially regulated by insulin and epidermal growth factor". J. Biol. Chem. 271 (41): 25533–8. doi:10.1074/jbc.271.41.25533. PMID8810325.
Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, Golemis EA, Griffin JD (1997). "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". J. Biol. Chem. 272 (22): 14320–6. doi:10.1074/jbc.272.22.14320. PMID9162067.
Leprince C, Romero F, Cussac D, Vayssiere B, Berger R, Tavitian A, Camonis JH (1997). "A new member of the amphiphysin family connecting endocytosis and signal transduction pathways". J. Biol. Chem. 272 (24): 15101–5. doi:10.1074/jbc.272.24.15101. PMID9182529.
Kouhara H, Hadari YR, Spivak-Kroizman T, Schilling J, Bar-Sagi D, Lax I, Schlessinger J (1997). "A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway". Cell. 89 (5): 693–702. doi:10.1016/S0092-8674(00)80252-4. PMID9182757.
Chin H, Saito T, Arai A, Yamamoto K, Kamiyama R, Miyasaka N, Miura O (1997). "Erythropoietin and IL-3 induce tyrosine phosphorylation of CrkL and its association with Shc, SHP-2, and Cbl in hematopoietic cells". Biochem. Biophys. Res. Commun. 239 (2): 412–7. doi:10.1006/bbrc.1997.7480. PMID9344843.
Zheng J, Chen RH, Corblan-Garcia S, Cahill SM, Bar-Sagi D, Cowburn D (1997). "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. 272 (48): 30340–4. doi:10.1074/jbc.272.48.30340. PMID9374522.
Li S, Kim M, Hu YL, Jalali S, Schlaepfer DD, Hunter T, Chien S, Shyy JY (1997). "Fluid shear stress activation of focal adhesion kinase. Linking to mitogen-activated protein kinases". J. Biol. Chem. 272 (48): 30455–62. doi:10.1074/jbc.272.48.30455. PMID9374537.
Curto M, Frankel P, Carrero A, Foster DA (1998). "Novel recruitment of Shc, Grb2, and Sos by fibroblast growth factor receptor-1 in v-Src-transformed cells". Biochem. Biophys. Res. Commun. 243 (2): 555–60. doi:10.1006/bbrc.1997.7982. PMID9480847.