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Sos-mediated activation of rac1 by p66shc
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 t...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063726/ https://www.ncbi.nlm.nih.gov/pubmed/16520382 http://dx.doi.org/10.1083/jcb.200506001 |
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author | Khanday, Firdous A. Santhanam, Lakshmi Kasuno, Kenji Yamamori, Tohru Naqvi, Asma DeRicco, Jeremy Bugayenko, Artem Mattagajasingh, Ilwola Disanza, Andrea Scita, Giorgio Irani, Kaikobad |
author_facet | Khanday, Firdous A. Santhanam, Lakshmi Kasuno, Kenji Yamamori, Tohru Naqvi, Asma DeRicco, Jeremy Bugayenko, Artem Mattagajasingh, Ilwola Disanza, Andrea Scita, Giorgio Irani, Kaikobad |
author_sort | Khanday, Firdous A. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2063726 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-20637262007-11-29 Sos-mediated activation of rac1 by p66shc Khanday, Firdous A. Santhanam, Lakshmi Kasuno, Kenji Yamamori, Tohru Naqvi, Asma DeRicco, Jeremy Bugayenko, Artem Mattagajasingh, Ilwola Disanza, Andrea Scita, Giorgio Irani, Kaikobad J Cell Biol Research Articles 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. The Rockefeller University Press 2006-03-13 /pmc/articles/PMC2063726/ /pubmed/16520382 http://dx.doi.org/10.1083/jcb.200506001 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Research Articles Khanday, Firdous A. Santhanam, Lakshmi Kasuno, Kenji Yamamori, Tohru Naqvi, Asma DeRicco, Jeremy Bugayenko, Artem Mattagajasingh, Ilwola Disanza, Andrea Scita, Giorgio Irani, Kaikobad Sos-mediated activation of rac1 by p66shc |
title | Sos-mediated activation of rac1 by p66shc |
title_full | Sos-mediated activation of rac1 by p66shc |
title_fullStr | Sos-mediated activation of rac1 by p66shc |
title_full_unstemmed | Sos-mediated activation of rac1 by p66shc |
title_short | Sos-mediated activation of rac1 by p66shc |
title_sort | sos-mediated activation of rac1 by p66shc |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063726/ https://www.ncbi.nlm.nih.gov/pubmed/16520382 http://dx.doi.org/10.1083/jcb.200506001 |
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