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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

SOCS-6 negatively regulates T cell activation through targeting p56lck to proteasomal degradation

Young Bong Choi1, Myoungsun Son, Mijin Park

  • 1Department of Life Science, Ewha Woman's University, 120-750 Seoul, Korea.

The Journal of Biological Chemistry
|December 17, 2009
PubMed

Insights

Suppressor of cytokine signaling-6 (SOCS-6) negatively regulates T cell activation by targeting the p56(lck) kinase. SOCS-6 promotes the degradation of active p56(lck), thereby inhibiting T cell receptor signaling.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • T cell receptor (TCR) signaling is critical for T cell activation.
  • p56(lck) is a key tyrosine kinase in TCR-mediated T cell activation.
  • Negative regulators of p56(lck) are important for controlling T cell responses.

Purpose of the Study:

  • To identify novel regulators of p56(lck).
  • To investigate the role of SOCS-6 in T cell activation.
  • To elucidate the mechanism by which SOCS-6 affects p56(lck).

Main Methods:

  • Yeast two-hybrid screening to identify p56(lck) interacting proteins.
  • Co-immunoprecipitation and confocal microscopy to study protein localization and interaction.
  • Western blotting to assess protein ubiquitination and degradation.
  • Reporter assays to measure TCR-dependent gene expression.

Main Results:

  • SOCS-6 binds to the active form of p56(lck) at the immunological synapse.
  • SOCS-6 promotes ubiquitination and proteasomal degradation of p56(lck).
  • SOCS-6 overexpression inhibits TCR-induced interleukin-2 promoter activity.

Conclusions:

  • SOCS-6 is a negative regulator of p56(lck) activity.
  • SOCS-6 controls T cell activation through ubiquitin-dependent proteolysis of p56(lck).
  • Targeting SOCS-6 may offer a strategy for modulating T cell responses.

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