PROTEIN-TYROSINE KINASES P53 56(LYN) AND P72(SYK) IN MHC CLASS-I-MEDIATED SIGNAL-TRANSDUCTION IN B-LYMPHOMA-CELLS/

Crosslinking of major histocompatibility complex class I (MHC-I) molec ules on the surface of human B lymphoma cells was shown to induce prot ein tyrosine phosphorylation and mobilization of intracellular free ca lcium, Immunoprecipitations indicated that the protein tyrosine kinase s p53/56(lyn) and p72(syk) are among the tyrosine-phosphorylated prote ins. The kinetics of phosphorylation of these kinases after MHC-I cros slinking differ from the kinetics observed after crosslinking of the B cell antigen receptor (SCR), Additional experiments were performed wi th chicken lyn- and syk-negative DT40 B cells and the results indicate that these two kinases have different substrate specificity and regul ate intracellular free calcium differently in response to MHC-I crossl inking. In addition MHC-I crosslinking of a sIgM-negative DT40 chicken B cell variant results in less activity of tyrosine kinases and less mobilization of intracellular free calcium compared with MHC-I crossli nking of wild-type DT40 cells, Thus, expression of BCR at the cell sur face is likely to be important for the signal cascade initiated by MHC -I crosslinking. Our data suggest that signal transduction initiated t hrough Ligation of the MHC-I molecule plays a role in the regulation o f B cell homeostasis. (C) 1998 Academic Press.