Sos-mediated activation of rac1 by p66shc

The Journal of Cell Biology
Firdous A KhandayKaikobad Irani

Abstract

The Son of Sevenless 1 protein (sos1) is a guanine nucleotide exchange factor (GEF) for either the ras or rac1 GTPase. We show that p66shc, an adaptor protein that promotes oxidative stress, increases the rac1-specific GEF activity of sos1, resulting in rac1 activation. P66shc decreases sos1 bound to the growth factor receptor bound protein (grb2) and increases the formation of the sos1-eps8-e3b1 tricomplex. The NH(2)-terminal proline-rich collagen homology 2 (CH2) domain of p66shc associates with full-length grb2 in vitro via the COOH-terminal src homology 3 (C-SH3) domain of grb2. A proline-rich motif (PPLP) in the CH2 domain mediates this association. The CH2 domain competes with the proline-rich COOH-terminal region of sos1 for the C-SH3 domain of grb2. P66shc-induced dissociation of sos1 from grb2, formation of the sos1-eps8-e3b1 complex, rac1-specific GEF activity of sos1, rac1 activation, and oxidative stress are also mediated by the PPLP motif in the CH2 domain. This relationship between p66shc, grb2, and sos1 provides a novel mechanism for the activation of rac1.

References

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Citations

Apr 14, 2007·Cell Death and Differentiation·K KasunoK Irani
Nov 7, 2009·The Journal of Biological Chemistry·Alexey A TomilovGino A Cortopassi
Mar 11, 2010·Antioxidants & Redox Signaling·Melanie Gertz, Clemens Steegborn
Aug 11, 2011·Human Molecular Genetics·Maria Grazia PesaresiMauro Cozzolino
Aug 22, 2009·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Ajay KumarKaikobad Irani
May 31, 2012·Molekuliarnaia biologiia·E R GalimovP M Chumakov
Nov 22, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Jin OshikawaMasuko Ushio-Fukai
Jun 5, 2012·American Journal of Physiology. Heart and Circulatory Physiology·Young-Rae KimKaikobad Irani
Jun 23, 2010·Cell Communication and Signaling : CCS·Muneesa BashirFirdous A Khanday
Mar 13, 2014·PloS One·Evgeny R GalimovPeter M Chumakov
Nov 13, 2008·Endocrine-related Cancer·Syed Mahfuzul AlamMing-Fong Lin
Oct 3, 2013·Neuromolecular Medicine·Muneesa BashirFirdous A Khanday
Dec 25, 2012·Cellular and Molecular Life Sciences : CMLS·Hina F BhatFirdous A Khanday
Mar 29, 2011·Journal of Renal Nutrition : the Official Journal of the Council on Renal Nutrition of the National Kidney Foundation·Michela ZanettiGianfranco Guarnieri
Oct 3, 2009·The EMBO Journal·Ning Sheng LiuWanjin Hong
Nov 17, 2009·Immunological Reviews·Francesca FinettiCosima T Baldari
Aug 5, 2010·American Journal of Medical Genetics. Part a·Mauro LongoniPaola Riva
Jul 27, 2011·Biochemical Pharmacology·Stéphane PierreXavier Coumoul
Jan 8, 2014·Molecular Carcinogenesis·Sakthivel MuniyanMing-Fong Lin
Aug 14, 2012·The International Journal of Biochemistry & Cell Biology·Magdalena LebiedzinskaMariusz R Wieckowski
Mar 7, 2013·Journal of Receptor and Signal Transduction Research·Deeba KirmaniFirdous A Khanday
Jun 2, 2007·Cell·Johannes L BosAlfred Wittinghofer
Jun 30, 2016·Antioxidants & Redox Signaling·Marten Hornsveld, Tobias B Dansen
Aug 2, 2013·Chemical Research in Toxicology·Vera Marisa CostaFernando Remião
Aug 26, 2014·Arteriosclerosis, Thrombosis, and Vascular Biology·Ajit VikramKaikobad Irani
May 16, 2019·The Journal of Biological Chemistry·Ryan C Killoran, Matthew J Smith
Jul 6, 2014·Physiological Reviews·Dmitry B ZorovSteven J Sollott
Nov 26, 2010·Biomarkers : Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals·Hina F BhatFirdous A Khanday
Jun 27, 2017·Frontiers in Oncology·Francesco Ciccarese, Vincenzo Ciminale
Mar 1, 2019·International Journal of Molecular Sciences·Stefano Ciciliot, Gian Paolo Fadini

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Methods Mentioned

BETA
nucleotide exchange
GTPase
targeted knockout
transfection
Coimmunoprecipitation
immunoprecipitations
flow cytometry

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