TAOK3, a Regulator of LCK-SHP-1 Crosstalk during TCR Signaling

Crit Rev Immunol. 2019;39(1):59-81. doi: 10.1615/CritRevImmunol.2019030480.

Abstract

Signaling from the T cell receptor for antigen turns on the physiological response of a T cell. The canonical TCR signaling pathway relies on early activation of the Src kinase LCK. This step initiates a cascade of events that lead not only to the phenotypic changes that characterize effector T cells but also to the activation of negative regulatory mechanisms that stop early TCR signaling. These mechanisms ensure qualitative and quantitative fine-tuning of T cell activation. The tyrosine phosphatase SHP-1 is a key player in the downregulation of LCK activation. In this review, we focus on the crosstalk between LCK and SHP-1 and, based on recent data, we introduce the putative kinase TAOK3 as an important regulator of this crosstalk. Given the widespread expression of TAOK3 and SHP-1, we propose that the function of TAOK3 extends beyond T cells and may be fundamental in the regulation of early signaling from receptors that utilize Src kinases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Lymphocyte Activation
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism*
  • Protein Serine-Threonine Kinases / metabolism*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / metabolism*
  • Receptor Cross-Talk
  • Receptors, Antigen, T-Cell / metabolism
  • Signal Transduction
  • T-Lymphocytes / immunology*

Substances

  • Receptors, Antigen, T-Cell
  • Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
  • Protein Serine-Threonine Kinases
  • TAOK3 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6

Grants and funding