Allosteric gating of Son of sevenless activity by the histone domain.

Proceedings of the National Academy of Sciences of the United States of America
Kamlesh K Yadav, D Bar-Sagi

Abstract

Regulated activation of Ras by receptor tyrosine kinases (RTK) constitutes a key transduction step in signaling processes that control an array of fundamental cellular functions including proliferation, differentiation, and survival. The principle mechanism by which Ras is activated down stream of RTKs involves the stimulation of guanine nucleotide exchange by the ubiquitous guanine nucleotide exchange factor Son of sevenless (Sos). In resting conditions, Sos activity is constrained by intramolecular interactions that maintain the protein in an autoinhibited conformation. Structural, biochemical, and genetic studies have implicated the histone domain (Sos-H), which comprises the most N-terminal region of Sos, in the regulation of Sos autoinhibition. However, the molecular underpinnings of this regulatory function are not well understood. In the present study we demonstrate that Sos-H possesses in vitro and in vivo membrane binding activity that is mediated, in part, by the interactions between a cluster of basic residues and phosphatidic acid. This interaction is required for Sos-dependent activation of Ras following EGF stimulation. The inducible association of Sos-H with membranes contributes to the catalytic activity of Sos ...Continue Reading

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Citations

Nov 26, 2013·Nature Methods·Antoine-Emmanuel SalibaAnne-Claude Gavin
Dec 23, 2011·Nature Reviews. Molecular Cell Biology·Ian M AhearnMark R Philips
May 25, 2010·Nature Structural & Molecular Biology·Jay T Groves, John Kuriyan
Sep 20, 2012·Journal of Lipid Research·Akua N RoachGuangwei Du
Dec 4, 2013·Proceedings of the National Academy of Sciences of the United States of America·Katja J GeißlerHelen Morrison
Mar 15, 2013·Proceedings of the National Academy of Sciences of the United States of America·Matthew J SmithMitsuhiko Ikura
Apr 8, 2016·Cellular Logistics·Tanmay Sanjeev ChavanVadim Gaponenko
Jan 28, 2016·Chemical Reviews·Shaoyong LuJian Zhang
Oct 29, 2015·Nature Reviews. Molecular Cell Biology·Antoine-Emmanuel SalibaAnne-Claude Gavin
Aug 9, 2016·Nature Structural & Molecular Biology·Sune M ChristensenJay T Groves
Apr 4, 2018·Cold Spring Harbor Perspectives in Medicine·Pradeep BandaruJohn Kuriyan
Aug 1, 2019·FEBS Letters·Mikhail A ZhukovskyCarmen Valente
Jul 1, 2020·Essays in Biochemistry·Sang-Chul Kim, Xuemin Wang
Aug 6, 2020·The Journal of Biological Chemistry·Hope Gloria UmutesiJongyun Heo
Jul 1, 2020·Circulation. Genomic and Precision Medicine·Jason R CowanRay E Hershberger
Jun 4, 2018·Cancer Metastasis Reviews·Alfredo Erazo-OliverasRobert S Chapkin
Apr 14, 2021·Current Opinion in Chemical Biology·Dirk KesslerDarryl B McConnell
Jul 3, 2021·International Journal of Molecular Sciences·Fernando C BaltanásEugenio Santos

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