REGULATION OF T-CELL ANTIGEN RECEPTOR SIGNALING BY SYK TYROSINE PROTEIN-KINASE

T-cell antigen receptor (TCR) signalling has been shown to involve two classes of tyrosine protein kinases: the Src-related kinases p56(lck) and p59(fynT), and the Zap-70/Syk family kinases, Lck and FynT are po stulated to initiate TCR-triggered signal transduction by phosphorylat ing the CD3 and zeta subunits of the TCR complex, This modification pe rmits the recruitment of Zap-70 and Syk, which are presumed to amplify the TCR-triggered signal, by phosphorylating additional intracellular proteins, While Zap-70 is expressed in all T cells, Syk is present in thymocytes and mature T-cell populations such as intraepithelial gamm a delta T cells and naive alpha beta T cells, To better understand the role of Syk in these cells, its impact on the physiology of an antige n-specific T-cell line,vas tested, Our results showed that compared to Zap-70 alone, Syk was a strong positive regulator of antigen receptor -induced signals in BI-141 cells, Surprisingly, they indicated that, l ike Src family kinases, Syk augmented TCR-triggered tyrosine phosphory lation of CD3/zeta, Syk, but not Zap-70 alone, could also stimulate ty rosine phosphorylation of a zeta-bearing chimera in transiently transf ected Cos-1 cells, Finally, evidence was provided that Syk has the cap acity to directly phosphorylate a zeta-derived peptide in vitro, These findings suggested that Syk may have a unique role in T cells, as a c onsequence of its ability to efficiently phosphorylate multiple compon ents of the TCR signalling cascade, Furthermore, they raised the possi bility that Syk can regulate the initiation of TCR signalling, by prom oting phosphorylation of the immunoreceptor tyrosine-based activation motifs of the TCR complex.