IL-2 STIMULATION OF T-LYMPHOCYTES INDUCES SEQUENTIAL ACTIVATION OF MITOGEN-ACTIVATED PROTEIN-KINASES AND PHOSPHORYLATION OF P56(LCK) AT SERINE-59

p56lck, a member of the src family of non-receptor protein tyrosine ki nases, is expressed almost exclusively in cells of lymphoid origin. p5 6lck is known to associate with the T lymphocyte surface glycoproteins CD4 and CD8, and plays a critical role in both T lymphocyte developme nt and activation. p56lck also associates with the beta-subunit of the IL-2R, and is activated when IL-2 binds to its receptor. Using primar y cultures of Con A-activated normal splenic mouse T lymphocytes, we o bserved an IL-2-induced sequence of events involving p56lck. We saw a rapid (within 1 to 2 min) and transient increase in p56lck kinase acti vity, which preceded the activation of both the p42erk-2 and p44erk-1 mitogen-activated protein kinases, maximal activation of which was obs erved after 10 min. We also observed an IL-2-induced shift in the elec trophoretic mobility of p56lck from an apparent molecular mass of 56 k Da (p56lck) to 60 kDa (p60lck), which reached a maximum at 15 min, the level of p60lck remaining constant for up to 4 h thereafter. This IL- 2-induced shift correlated with the phosphorylation of serine-59 of p5 6lck, a site that mitogen-activated protein kinases are capable of mod ifying in vitro. The implications of these results for the understandi ng of both p56lck function and lymphoid cell receptor signaling pathwa ys are discussed.