Jm. Ashe et al., ZAP-70 protein promotes tyrosine phosphorylation of T cell receptor signaling motifs (ITAMs) in immature CD4(+)8(+) thymocytes with limiting p56(lck), J EXP MED, 189(7), 1999, pp. 1163-1167
As a result of interaction with epithelial cells in the thymic cortex, imma
ture CD4(+)8(+) (double positive, DP) thymocytes express relatively few T c
ell receptors (TCRs) and contain diminished numbers of coreceptor-associate
d p56(lck) (lck) PTK molecules. As a result, TCR signal transduction in DP
thymocytes is significantly impaired, despite its importance for repertoire
selection. We report here that, ill DP thymocytes, tyrosine phosphorylatio
n of TCR signaling motifs (ITAMs) by Ick, an early event in TCR signal tran
sduction, is dependent upon ZAP-70 protein independent of ZAP-70's kinase a
ctivity. Furthermore, the: dependence on ZAP-70 protein for ITAM phosphoryl
ation diminishes as available Ick increases. Importantly, ZAP-70's role in
ITAM phosphorylation in DP thymocytes is not limited to protecting phosphor
ylated ITAMs from dephosphorylation. Rather, this study indicates that ZAP-
70 protein augments ITAM phosphorylation in DP thymocytes and so compensate
s in part for the relative deficiency of coreceptor-associated Ick.