SEQUENTIAL INTERACTIONS OF THE TCR WITH 2 DISTINCT CYTOPLASMIC TYROSINE KINASES

The T cell antigen receptor (TCR) initiates signals by interacting wit h cytoplasmic protein tyrosine kinases (PTKs) through a 17-residue seq uence motif [called the antigen recognition activation motif (ARAM)] t hat is contained in the TCRzeta and CD3 chains. TCR stimulation induce s the tyrosine phosphorylation of several cellular substrates, includi ng the ARAMs. Lck kinase activity is required for phosphorylation of t wo conserved tyrosine residues in an ARAM. This phosphorylation leads to the recruitment of a second cytoplasmic PTK, ZAP-70, through both o f 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.