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Real-time Live Imaging of T-cell Signaling Complex Formation
10:31

Real-time Live Imaging of T-cell Signaling Complex Formation

Published on: June 23, 2013

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

Jaeyul Kwon1, Cheng-Kui Qu, Jin-Soo Maeng

  • 1Department of Microbiology and Immunology, University of Maryland School of Medicine, Rockville, MD 20855, USA.

The EMBO Journal
|June 4, 2005
PubMed

Insights

Reactive oxygen species (ROS) regulate T-cell receptor (TCR) signaling by oxidizing and inactivating SHP-2 phosphatase. This redox-dependent inactivation of SHP-2 promotes T-cell adhesion via SLP-76 signaling.

Area of Science:

  • Immunology
  • Cell Signaling
  • Redox Biology

Background:

  • Receptor-stimulated reactive oxygen species (ROS) production influences cell signaling pathways.
  • The precise mechanisms by which ROS modulate signal transduction remain incompletely understood.
  • Oxidation of protein tyrosine phosphatases (PTPs) is a potential mechanism for ROS-mediated signaling regulation.

Purpose of the Study:

  • To investigate the role of ROS in T-cell receptor (TCR) signaling.
  • To determine the effect of TCR activation-induced ROS on SHP-2 phosphatase activity.
  • To elucidate the downstream signaling events regulated by SHP-2 in a redox-dependent manner.

Main Methods:

  • T-cell activation assays.
  • Immunoprecipitation to assess protein complex formation.
  • Western blotting to analyze protein phosphorylation.
  • Redox-sensitive assays to detect PTP oxidation.

Main Results:

  • TCR activation leads to ROS generation and transient inactivation of SHP-2, but not SHP-1.
  • SHP-2 is recruited to the LAT-Gads-SLP-76 complex upon TCR stimulation.
  • SHP-2 directly regulates Vav1 and ADAP phosphorylation, and ADAP-SLP-76 association in a redox-dependent manner.
  • TCR-mediated ROS generation results in SHP-2 oxidation.

Conclusions:

  • TCR-mediated ROS generation causes SHP-2 oxidation and inactivation.
  • Oxidized SHP-2 promotes T-cell adhesion through modulation of the SLP-76 signaling pathway.
  • This study reveals a novel mechanism for redox regulation of T-cell signaling and adhesion.

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