PHOSPHORYLATION OF SERINE-59 OF P56(LCK) IN ACTIVATED T-CELLS

p56lck, a member of the src family of non-receptor protein tyrosine ki nases, is expressed almost exclusively in cells of lymphoid origin. Re cent evidence has implicated p56lck in a critical role both in T cell development and activation. A variety of T cell stimuli induce a shift in the electrophoretic mobility of p56lck from an apparent molecular mass of 56 kDa (p56lck) to 60 kDa (p60lck). This shift in electrophore tic mobility correlates with an increase in the phosphoserine content of the p60lck. We have shown that both 4alpha-phorbol 12beta-myristate acetate and OKT3 treatment of Jurkat cells, as well as 4alpha-phorbol 12beta-myristate acetate treatment of 171.CD4 and LSTRA cells, induce d phosphorylation of serine-59 on p56lck in vivo, which correlated wit h the shift to p60lck. We also demonstrated that the same serine resid ue could be phosphorylated in vitro with mitogen-activated protein kin ases and that this event was capable of reducing p56lck activity in vi tro. Combined, these data suggest a novel pathway for the in vivo regu lation of p56lck activity.