Sequential interactions of the TCR with two distinct cytoplasmic tyrosine kinases

Makio Iwashima, Bryan A. Irving, Nicolai S C Van Oers, Andrew C. Chan, Arthur Weiss

Research output: Contribution to journalArticle

609 Scopus citations


The T cell antigen receptor (TCR) initiates signals by interacting with cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue sequence motif [called the antigen recognition activation motif (ARAM)] that is contained in the TCRζ and CD3 chains. TCR stimulation induces the tyrosine phosphorylation of several cellular substrates, including the ARAMs. Lck kinase activity is required for phosphorylation of two conserved tyrosine residues in an ARAM. This phosphorylation leads to the recruitment of a second cytoplasmic PTK, ZAP-70, through both of the ZAP-70 Src homology 2 domains and its phosphorylation. Thus, TCR signal transduction is initiated by the sequential interaction of two PTKs with TCR ARAMs.

Original languageEnglish (US)
Pages (from-to)1136-1139
Number of pages4
Issue number5150
StatePublished - Jan 1 1994

ASJC Scopus subject areas

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