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Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP.

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.

SUBMITTER: Kwon J

PROVIDER: S-EPMC1173147 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

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Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP.

Kwon Jaeyul J Qu Cheng-Kui CK Maeng Jin-Soo JS Falahati Rustom R Lee Chunghee C Williams Mark S MS

The EMBO journal 20050602 13

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 ...[more]

PMID: 15933714

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