The 21-and 23-kD forms of TCR zeta are generated by specific ITAM phosphorylations

The T cell receptor (TCR) zeta subunit contains three immunoreceptor tyrosi ne-based activation motifs (ITAMs) that translate effective extracellular l igand binding into intracellular signals by becoming phosphorylated into 21 - and 23-kD forms. We report here that the 21-kD form of TCR zeta is genera ted by phosphorylation of the tyrosines in the second and third ITAMs, wher eas the 23-kD form is formed by the additional phosphorylation of the membr ane-proximal ITAM tyrosines. The stable formation of the 21- and 23-kD spec ies requires the binding of the tandem SH2 domains of ZAP-70. We also repor t that TCR-mediated signaling processes can proceed independently of either the 21- or 23-kD species of TCR zeta.