Article
- The EMBO Journal (2005) 24, 2331 - 2341
- doi:10.1038/sj.emboj.7600706
Published online: 2 June 2005
Subject Categories:
Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76–ADAP
Jaeyul Kwon1, Cheng-Kui Qu2, Jin-Soo Maeng3, Rustom Falahati4, Chunghee Lee5 and Mark S Williams1
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Rockville, MD, USA
- Department of Pathology, University of Maryland School of Medicine, Rockville, MD, USA
- Laboratory of Biophysical Chemistry, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
- Department of Immunology, George Washington University School of Medicine, Washington, DC, USA
- Veritas Inc., Rockville, MD, USA
Correspondence to:
Mark S Williams, Department of Microbiology and Immunology, University of Maryland School of Medicine, 15601 Crabbs Branch Way, Rockville, MD 20855, USA. Tel.: +1 301 738 0468; Fax: +1 301 517 0344; E-mail: willmark@usa.redcross.org
Received 26 January 2005; Accepted 11 May 2005
Abstract
Receptor-stimulated generation of intracellular reactive oxygen species (ROS) modulates signal transduction, although the mechanism(s) is unclear. One potential basis is the reversible oxidation of the active site cysteine of protein tyrosine phosphatases (PTPs). Here, we show that activation of the antigen receptor of T cells (TCR), which induces production of ROS, induces transient inactivation of the SH2 domain-containing PTP, SHP-2, but not the homologous SHP-1. SHP-2 is recruited to the LAT–Gads–SLP-76 complex and directly regulates the phosphorylation of key signaling proteins Vav1 and ADAP. Furthermore, the association of ADAP with the adapter SLP-76 is regulated by SHP-2 in a redox-dependent manner. The data indicate that TCR-mediated ROS generation leads to SHP-2 oxidation, which promotes T-cell adhesion through effects on an SLP-76-dependent signaling pathway to integrin activation.
Keywords:
- adhesion,
- reactive oxygen species,
- protein tyrosine phosphatase,
- signal transduction,
- T lymphocyte
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