ACTIVATION OF SRC FAMILY KINASE LCK FOLLOWING CD28 CROSS-LINKING IN THE JURKAT LEUKEMIC-CELL LINE

T lymphocytes require a signal via their antigen specific receptors (t he T cell receptors) and an antigen independent costimulatory signal. Signals through CD28 can costimulate T cells in the presence of limiti ng amounts of T cell receptor signal, or in the presence of PMA, provi ding this second signal. CD28 signaling is known to involve the activa tion of protein tyrosine kinases. Using the Jurkat leukemic cell line as a model, we have tested CD28 crosslinking for its effects on the pr otein tyrosine kinases p56lck. We report that following crosslinking o f CD28, p56lck kinase activity is increased. Crosslinking CD28 causes a shift in the relative mobility of p56lck from 56 to 60 kD similar to that seen after crosslinking of CD2 and CD4, cell surface receptors k nown to be associate with and activate p56lck. Finally, lck could be f ound in anti-CD28 immunoprecipitates in exponentially growing Jurkat a nd in ''activated'' CD28 (i.e., cross linked), but not in CD28 in rest ing Jurkat cells. These findings suggest an important role for p56lck in CD28 signal transduction. (C) 1994 Academic Press, Inc.