LAT: a T lymphocyte adapter protein that couples the antigen receptor to downstream signaling pathways

Connie L Sommers1, Lawrence E Samelson, Paul E Love

  • 1Laboratory of Cellular and Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4255, USA. connies@helix.nih.gov

Insights

Adapter proteins like LAT integrate multiple signaling pathways during T-cell activation. Structure/function studies reveal LAT

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Adapter proteins link cell surface receptors to intracellular signaling cascades.
  • T-cell activation relies on complex signaling networks involving multiple protein tyrosine kinases.

Purpose of the Study:

  • To investigate the role of the adapter protein LAT (Linker for Activation of T cells) in integrating T-cell signaling pathways.
  • To elucidate the structure-function relationship of LAT in T-cell development and effector function.

Main Methods:

  • Expression of specific LAT point mutations in vivo.
  • Analysis of downstream signaling pathway activation (e.g., PLC-gamma1, Ca2+ influx, PKC, Ras/Erk).

Main Results:

  • LAT acts as a central integration point for multiple distal signaling pathways.
  • Specific LAT mutations alter the integration of these pathways, affecting T-cell function.
  • Demonstrated the critical role of LAT in linking T-cell receptor activation to downstream signaling.

Conclusions:

  • The LAT adapter protein is crucial for integrating diverse signaling pathways essential for T-cell function.
  • These findings highlight the importance of adapter molecules in signal transduction and suggest potential therapeutic targets.
  • Similar regulatory mechanisms may exist in other signaling systems utilizing adapter proteins.

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