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Receptor‐stimulated oxidation of SHP‐2 promotes T‐cell adhesion through SLP‐76–ADAP
Author(s) -
Kwon Jaeyul,
Qu ChengKui,
Maeng JinSoo,
Falahati Rustom,
Lee Chunghee,
Williams Mark S
Publication year - 2005
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600706
Subject(s) - biology , microbiology and biotechnology , protein tyrosine phosphatase , signal transduction , t cell receptor , phosphorylation , reactive oxygen species , tyrosine phosphorylation , integrin , signal transducing adaptor protein , cell adhesion , tyrosine , receptor , biochemistry , t cell , cell , immunology , immune system
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.