Sos-mediated activation of rac1 by p66shc

Firdous A Khanday; Lakshmi Santhanam; Kenji Kasuno; Tohru Yamamori; Asma Naqvi; Jeremy Dericco; Artem Bugayenko; Ilwola Mattagajasingh; Andrea Disanza; Giorgio Scita; Kaikobad Irani

doi:10.1083/jcb.200506001

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Sos-mediated activation of rac1 by p66shc

Journal article

Open access

Peer reviewed

Sos-mediated activation of rac1 by p66shc

Firdous A Khanday, Lakshmi Santhanam, Kenji Kasuno, Tohru Yamamori, Asma Naqvi, Jeremy Dericco, Artem Bugayenko, Ilwola Mattagajasingh, Andrea Disanza, Giorgio Scita, …

The Journal of cell biology, Vol.172(6), pp.817-822

03/13/2006

DOI: 10.1083/jcb.200506001

PMCID: PMC2063726

PMID: 16520382

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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.

Adaptor Proteins, Signal Transducing - chemistry

Cytoskeletal Proteins

Cercopithecus aethiops

Macromolecular Substances - chemistry

GRB2 Adaptor Protein - genetics

Fibroblasts

Shc Signaling Adaptor Proteins

Cells, Cultured

Models, Molecular

Son of Sevenless Proteins - genetics

Son of Sevenless Proteins - metabolism

GRB2 Adaptor Protein - chemistry

Down-Regulation - genetics

Mice, Knockout

Amino Acid Motifs - physiology

Animals

Src Homology 2 Domain-Containing, Transforming Protein 1

Adaptor Proteins, Signal Transducing - genetics

Mice

Adaptor Proteins, Signal Transducing - metabolism

Enzyme Activation - genetics

GRB2 Adaptor Protein - metabolism

COS Cells

Macromolecular Substances - metabolism

rac1 GTP-Binding Protein - metabolism

Protein Structure, Tertiary - physiology

rac1 GTP-Binding Protein - genetics

Details

Title: Subtitle: Sos-mediated activation of rac1 by p66shc
Creators: Firdous A Khanday - Cardiovascular Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA
Lakshmi Santhanam
Kenji Kasuno
Tohru Yamamori
Asma Naqvi
Jeremy Dericco
Artem Bugayenko
Ilwola Mattagajasingh
Andrea Disanza
Giorgio Scita
Kaikobad Irani
Resource Type: Journal article
Publication Details: The Journal of cell biology, Vol.172(6), pp.817-822
Publisher: United States
DOI: 10.1083/jcb.200506001
PMID: 16520382
PMCID: PMC2063726
ISSN: 0021-9525
eISSN: 1540-8140
Grant note: R01 HL070929 / NHLBI NIH HHS P01 HL065608 / NHLBI NIH HHS P01HL065608 / NHLBI NIH HHS R01HL070929 / NHLBI NIH HHS
Language: English
Date published: 03/13/2006
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047745902771

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