IL-2 stimulation of T lymphocytes induces sequential activation of mitogen-activated protein kinases and phosphorylation of p56lck at serine-59.

p56lck, a member of the src family of non-receptor protein tyrosine kinases, is expressed almost exclusively in cells of lymphoid origin. p56lck is known to associate with the T lymphocyte surface glycoproteins CD4 and CD8, and plays a critical role in both T lymphocyte development and activation. p56lck also associates with the beta-subunit of the IL-2R, and is activated when IL-2 binds to its receptor. Using primary cultures of Con A-activated normal splenic mouse T lymphocytes, we observed an IL-2-induced sequence of events involving p56lck. We saw a rapid (within 1 to 2 min) and transient increase in p56lck kinase activity, which preceded the activation of both the p42erk-2 and p44erk-1 mitogen-activated protein kinases, maximal activation of which was observed after 10 min. We also observed an IL-2-induced shift in the electrophoretic mobility of p56lck from an apparent molecular mass of 56 kDa (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 p56lck, a site that mitogen-activated protein kinases are capable of modifying in vitro. The implications of these results for the understanding of both p56lck function and lymphoid cell receptor signaling pathways are discussed.