The role of protein tyrosine kinase and protein tyrosine phosphatases in T cell antigen receptor signal transduction

Andrew C. Chan, Dev M. Desai, Arthur Weiss

Research output: Contribution to journalReview article

490 Scopus citations

Abstract

Engagement of the T cell antigen receptor (TCR) by peptide antigen bound to the major histocompatibility complex (MHC) molecules initiates a biochemical cascade involving protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). Recent biochemical and genetic evidence has implicated at least three cytoplasmic protein tyrosine kinases (PTKs), Lck, Fyn, and ZAP-70, that are involved in the initiation of TCR signal transduction. In addition, genetic evidence has demonstrated the requirement of the transmembrane PTPase, CD45, for TCR function. Activation of T cells through the TCR represents an alteration in the dynamic equilibrium between PTKs and PTPases. The TCR is a multi-subunit complex composed of at least six different gene products. Dissection of the TCR utilizing chimeric receptors and TCR mutants has demonstrated that the multi-subunit receptor is composed of at least two signal transducing modules, the CD3 and the ζ chain subunits. These two modules have in common peptide sequences within their cytoplasmic domains termed antigen recognition activation motifs (ARAMs) that are responsible for transducing signaling events. Moreover, the ARAM sequence is also found in subunits associated with a variety of other hematopoietic cell antigen receptors and is likely to form the basis for interactions with effector molecules within the signaling cascades of these receptors. Here we review the mechanism by which the ARAM sequences interact with PTKs and the cascades of PTKs and PTPases that are involved in mediating TCR function.

Original languageEnglish (US)
Pages (from-to)555-592
Number of pages38
JournalAnnual review of immunology
Volume12
DOIs
StatePublished - Jan 1 1994

Keywords

  • T cell antigen receptor
  • protein tyrosine kinases
  • protein tyrosine phosphatases
  • signal transduction

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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