FUNCTIONAL DISSECTION OF P56(LCK), A PROTEIN-TYROSINE KINASE WHICH MEDIATES INTERLEUKIN-2-INDUCED ACTIVATION OF THE C-FOS GENE

Members of the newly identified receptor family for cytokines characte ristically lack the intrinsic protein tyrosine kinase domain that is a hallmark of other growth factor receptors, Instead, accumulating evid ence suggests that these receptors utilize nonreceptor-type protein ty rosine kinases for downstream signal transduction by cytokines. We hav e shown previously that the interleukin-2 receptor beta-chain interact s both physically and functionally with a Src family member, p56(lck), and that p56(lck) activation leads to induction of the c-fos gene. Ho wever, the mechanism linking p56(lck) activation with c-fos induction remains unelucidated. In the present study, we systematically examined the extent of c-fos promoter activation hv expression of a series of p56(lck) mutants, using a transient cotransfection assay. The results define a set of the essential amino acid residues that regulate p56(lc k) induction of the c-fos promoter. We also provide evidence that the serum-responsive element and sis-inducible element are both targets th rough which p56(lck) controls c-fos gene activation.