Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene.[5][6]
Function
editSOS1 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. 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 (not to be confused with the S. pombe Cdc25). 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.[7]
Clinical significance
editRecent studies also show that mutations in Sos1 can cause Noonan syndrome[8] and hereditary gingival fibromatosis type 1.[9] Noonan syndrome has also been shown to be caused by mutations in KRAS and PTPN11 genes.[10] activators of the MAP kinase pathway.
Inhibitors and activators
editIn 2019, the first SOS1 inhibitor, BAY-293,[11] was published which met the quality criteria for a 'Donated Chemical Probe' as defined by the Structural Genomics Consortium.[12] Shortly after, the discovery of BI-3406[13][14] was published.
In 2018, Fesik et al. reported the discovery of benzimidazole-derived SOS1 activators[15] (e.g. VUBI1).
Interactions
editSOS1 has been shown to interact with:
- ABI1,[16]
- BCR gene,[17][18]
- CRK,[19]
- EPS8,[16][20]
- Epidermal growth factor receptor,[21][22][23]
- FRS2,[24][25][26]
- Grb2,[17][19][21][24][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43]
- HRAS,[44][45]
- ITSN1,[37]
- MUC1,[28][46]
- NCK1,[19][47][48][49]
- PLCG1,[50][51]
- PTPN11,[27][52]
- SH3KBP1,[53] and
- SHC1.[22][25][27][40] and
See also
editReferences
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- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000024241 – Ensembl, May 2017
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Further reading
edit- Lioubin MN, Myles GM, Carlberg K, Bowtell D, Rohrschneider LR (September 1994). "Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated protein form complexes with Fms in hematopoietic cells". Molecular and Cellular Biology. 14 (9): 5682–5691. doi:10.1128/mcb.14.9.5682. PMC 359093. PMID 7520523.
- 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". The Journal of Biological Chemistry. 270 (31): 18428–18436. doi:10.1074/jbc.270.31.18428. PMID 7629168.
- Pandey P, Kharbanda S, Kufe D (September 1995). "Association of the DF3/MUC1 breast cancer antigen with Grb2 and the Sos/Ras exchange protein". Cancer Research. 55 (18): 4000–4003. PMID 7664271.
- Hu Q, Milfay D, Williams LT (March 1995). "Binding of NCK to SOS and activation of ras-dependent gene expression". Molecular and Cellular Biology. 15 (3): 1169–1174. doi:10.1128/MCB.15.3.1169. PMC 230339. PMID 7862111.
- Puil L, Liu J, Gish G, Mbamalu G, Bowtell D, Pelicci PG, et al. (February 1994). "Bcr-Abl oncoproteins bind directly to activators of the Ras signalling pathway". The EMBO Journal. 13 (4): 764–773. doi:10.1002/j.1460-2075.1994.tb06319.x. PMC 394874. PMID 8112292.
- Li N, Batzer A, Daly R, Yajnik V, Skolnik E, Chardin P, et al. (May 1993). "Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling". Nature. 363 (6424): 85–88. Bibcode:1993Natur.363...85L. doi:10.1038/363085a0. PMID 8479541. S2CID 4323174.
- Chardin P, Camonis JH, Gale NW, van Aelst L, Schlessinger J, Wigler MH, Bar-Sagi D (May 1993). "Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2". Science. 260 (5112): 1338–1343. Bibcode:1993Sci...260.1338C. doi:10.1126/science.8493579. PMID 8493579.
- Sadoshima J, Izumo S (February 1996). "The heterotrimeric G q protein-coupled angiotensin II receptor activates p21 ras via the tyrosine kinase-Shc-Grb2-Sos pathway in cardiac myocytes". The EMBO Journal. 15 (4): 775–787. doi:10.1002/j.1460-2075.1996.tb00413.x. PMC 450276. PMID 8631299.
- Feng GS, Ouyang YB, Hu DP, Shi ZQ, Gentz R, Ni J (May 1996). "Grap is a novel SH3-SH2-SH3 adaptor protein that couples tyrosine kinases to the Ras pathway". The Journal of Biological Chemistry. 271 (21): 12129–12132. doi:10.1074/jbc.271.21.12129. PMID 8647802.
- Okada 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". The Journal of Biological Chemistry. 271 (41): 25533–25538. doi:10.1074/jbc.271.41.25533. PMID 8810325.
- Corbalan-Garcia S, Yang SS, Degenhardt KR, Bar-Sagi D (October 1996). "Identification of the mitogen-activated protein kinase phosphorylation sites on human Sos1 that regulate interaction with Grb2". Molecular and Cellular Biology. 16 (10): 5674–5682. doi:10.1128/MCB.16.10.5674. PMC 231567. PMID 8816480.
- Sattler M, Salgia R, Shrikhande G, Verma S, Uemura N, Law SF, et al. (May 1997). "Differential signaling after beta1 integrin ligation is mediated through binding of CRKL to p120(CBL) and p110(HEF1)". The Journal of Biological Chemistry. 272 (22): 14320–14326. doi:10.1074/jbc.272.22.14320. hdl:20.500.12613/9173. PMID 9162067.
- Leprince C, Romero F, Cussac D, Vayssiere B, Berger R, Tavitian A, Camonis JH (June 1997). "A new member of the amphiphysin family connecting endocytosis and signal transduction pathways". The Journal of Biological Chemistry. 272 (24): 15101–15105. doi:10.1074/jbc.272.24.15101. PMID 9182529.
- 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. PMID 9182757. S2CID 2187363.
- Chin 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". Biochemical and Biophysical Research Communications. 239 (2): 412–417. doi:10.1006/bbrc.1997.7480. PMID 9344843.
- Zheng J, Chen RH, Corblan-Garcia S, Cahill SM, Bar-Sagi D, Cowburn D (November 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". The Journal of Biological Chemistry. 272 (48): 30340–30344. doi:10.1074/jbc.272.48.30340. PMID 9374522.
- Li S, Kim M, Hu YL, Jalali S, Schlaepfer DD, Hunter T, et al. (November 1997). "Fluid shear stress activation of focal adhesion kinase. Linking to mitogen-activated protein kinases". The Journal of Biological Chemistry. 272 (48): 30455–30462. doi:10.1074/jbc.272.48.30455. PMID 9374537.
- Qian X, Vass WC, Papageorge AG, Anborgh PH, Lowy DR (February 1998). "N terminus of Sos1 Ras exchange factor: critical roles for the Dbl and pleckstrin homology domains". Molecular and Cellular Biology. 18 (2): 771–778. doi:10.1128/mcb.18.2.771. PMC 108788. PMID 9447973.
- Curto M, Frankel P, Carrero A, Foster DA (February 1998). "Novel recruitment of Shc, Grb2, and Sos by fibroblast growth factor receptor-1 in v-Src-transformed cells". Biochemical and Biophysical Research Communications. 243 (2): 555–560. doi:10.1006/bbrc.1997.7982. PMID 9480847.
External links
edit- GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
- http://www.noonansyndrome.org
- http://ghr.nlm.nih.gov/gene=sos1
This article incorporates text from the United States National Library of Medicine, which is in the public domain.