| First Author | Khanday FA | Year | 2006 |
| Journal | J Cell Biol | Volume | 172 |
| Issue | 6 | Pages | 817-22 |
| PubMed ID | 16520382 | Mgi Jnum | J:107918 |
| Mgi Id | MGI:3622518 | Doi | 10.1083/jcb.200506001 |
| Citation | Khanday FA, et al. (2006) Sos-mediated activation of rac1 by p66shc. J Cell Biol 172(6):817-22 |
| abstractText | 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. |
