New work shows that activation of the Ras guanine nucleotide exchange factor SOS is dependent upon the membrane density of phosphatidylinositol-4,5-bisphosphate (PIP2) and GTP-bound Ras. These signals synergize to release the autoinhibitory DH-PH domain, while the histone domain fine-tunes SOS activation in response to PIP2.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation
Cancer and Metastasis Reviews Open Access 16 September 2020
-
Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate
Nature Communications Open Access 28 April 2017
-
Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma
BMC Research Notes Open Access 06 January 2014
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Gureasko, J. et al. Nat. Struct. Mol. Biol. 15, 452–461 (2008).
Margarit, S.M. et al. Cell 112, 685–695 (2003).
Sondermann, H. et al. Cell 119, 393–405 (2004).
Boykevisch, S. et al. Curr. Biol. 16, 2173–2179 (2006).
Roberts, A.E. et al. Nat. Genet. 39, 70–74 (2007).
Tartaglia, M. et al. Nat. Genet. 39, 75–79 (2007).
Sondermann, H., Nagar, B., Bar-Sagi, D. & Kuriyan, J. Proc. Natl. Acad. Sci. USA 102, 16632–16637 (2005).
Tian, T. et al. Nat. Cell Biol. 9, 905–914 (2007).
Egan, S.E. et al. Nature 363, 45–51 (1993).
Olivier, J.P. et al. Cell 73, 179–191 (1993).
Rozakis-Adcock, M., Fernley, R., Wade, J., Pawson, T. & Bowtell, D. Nature 363, 83–85 (1993).
Houtman, J.C. et al. Nat. Struct. Mol. Biol. 13, 798–805 (2006).
Roose, J.P., Mollenauer, M., Ho, M., Kurosaki, T. & Weiss, A. Mol. Cell. Biol. 27, 2732–2745 (2007).
Corbalan-Garcia, S., Margarit, S.M., Galron, D., Yang, S.S. & Bar-Sagi, D. Mol. Cell. Biol. 18, 880–886 (1998).
Aronheim, A. et al. Cell 78, 949–961 (1994).
Zhao, C., Du, G., Skowronek, K., Frohman, M.A. & Bar-Sagi, D. Nat. Cell Biol. 9, 706–712 (2007).
Kim, A.S., Kakalis, L.T., Abdul-Manan, N., Liu, G.A. & Rosen, M.K. Nature 404, 982–986 (2000).
Tehrani, S., Tomasevic, N., Weed, S., Sakowicz, R. & Cooper, J.A. Proc. Natl. Acad. Sci. USA 104, 11933–11938 (2007).
Papayannopoulos, V. et al. Mol. Cell 17, 181–191 (2005).
Acknowledgements
We thank O. Rocks and I. Blasutig for helpful discussions.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Findlay, G., Pawson, T. How is SOS activated? Let us count the ways. Nat Struct Mol Biol 15, 538–540 (2008). https://doi.org/10.1038/nsmb0608-538
Issue Date:
DOI: https://doi.org/10.1038/nsmb0608-538
This article is cited by
-
Novel regulation of Ras proteins by direct tyrosine phosphorylation and dephosphorylation
Cancer and Metastasis Reviews (2020)
-
Mechanism of SOS PR-domain autoinhibition revealed by single-molecule assays on native protein from lysate
Nature Communications (2017)
-
One-way membrane trafficking of SOS in receptor-triggered Ras activation
Nature Structural & Molecular Biology (2016)
-
Expressions and clinical significances of c-MET, p-MET and E2f-1 in human gastric carcinoma
BMC Research Notes (2014)
-
Sequence analysis of the Ras-MAPK pathway genes SOS1, EGFR & GRB2 in silver foxes (Vulpes vulpes): candidate genes for hereditary hyperplastic gingivitis
Genetica (2014)
