PROTEIN-TYROSINE KINASES SYK AND ZAP-70 DISPLAY DISTINCT REQUIREMENTSFOR SRC FAMILY KINASES IN IMMUNE-RESPONSE RECEPTOR SIGNAL-TRANSDUCTION

Engagement of immunoreceptors in hemopoietic cells leads to activation of Src family tyrosine kinases as well as Syk or ZAP-70. Current mode ls propose that Src family kinases are critical in immune response sig nal transduction through their role in phosphorylation of tyrosine res idues within immunoreceptor tyrosine activation motifs (ITAMs; which r ecruit the SH2 domains of Syk or ZAP-70) and by direct phosphorylation of Syk and ZAP-70. Several lines of evidence suggest that Syk may not show the same dependence on activation by Src family kinases as ZAP-7 0. In this report, we used COS cells transiently transfected with comp onents of the Fc epsilon RI complex (Lyn, Syk, and a chimeric CD8 rece ptor containing the cytoplasmic domain of the gamma subunit of Fc epsi lon RI (CD8-gamma)) to examine the regulation of Syk activity; Syk was activated and phosphorylated in COS cells cotransfected with Lyn; how ever, in cells expressing CD8-gamma, activation of Syk and phosphoryla tion of CD8-gamma did not require coexpression of Lyn. Additional expe riments indicate that gamma phosphorylation is dependent on Syk kinase activity and is independent of endogenous COS cell kinases. In parall el experiments, ZAP-70 was not activated by cotransfection with CD8-ga mma, nor was CD8-gamma phosphorylated when coexpressed with ZAP-70 alo ne. Taken together, these studies indicate that Syk can be distinguish ed from ZAP-70 in its ability to be activated by coexpression with an ITAM-cantaining receptor without coexpression of a Src family kinase, and that Syk is capable of phosphorylating ITAM tyrosines under certai n experimental conditions.