The role of membrane-associated adaptors in T cell receptor signalling

W Zhang1, L E Samelson

  • 1Laboratory of Cellular and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Seminars in Immunology
|March 21, 2000
PubMed

Insights

Membrane-associated adaptor proteins are crucial for T cell activation. LAT (linker for activation of T cells), TRIM (T cell receptor interacting molecule), and SIT (SHP2-interacting transmembrane adaptor protein) are key players in T cell receptor signaling pathways.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • T cell receptor (TCR) engagement initiates signaling cascades involving tyrosine kinases and intracellular protein phosphorylation.
  • Membrane-associated adaptor proteins are critical for linking TCR ligation to downstream signaling pathways.
  • Several novel adaptor proteins have been identified, highlighting their importance in T cell activation.

Purpose of the Study:

  • To elucidate the role of membrane-associated adaptor proteins in T cell activation.
  • To investigate the function of LAT (linker for activation of T cells) in TCR signaling.
  • To explore the potential roles of TRIM (T cell receptor interacting molecule) and SIT (SHP2-interacting transmembrane adaptor protein) in T cell signaling.

Main Methods:

  • Study of LAT-deficient cell lines and LAT-deficient mice to assess functional importance.
  • Identification and characterization of novel adaptor proteins like TRIM and SIT.
  • Analysis of protein-protein interactions and signaling pathway involvement.

Main Results:

  • LAT adaptor protein, upon phosphorylation, associates with Grb2, Gads, and PLC-gamma 1, mediating TCR signaling.
  • Studies using LAT-deficient models confirm its essential role in T cell activation.
  • TRIM and SIT are identified as novel adaptors that associate with PI3K and SHP2, respectively, post-TCR activation.

Conclusions:

  • Membrane-associated adaptor proteins, including LAT, TRIM, and SIT, are indispensable for effective T cell receptor signaling.
  • LAT plays a central role by recruiting key signaling molecules following TCR engagement.
  • TRIM and SIT represent newly discovered components that likely contribute to the intricate TCR signaling network.

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