INTERLEUKIN-2 ACTIVATES STAT5 TRANSCRIPTION FACTOR (MAMMARY-GLAND FACTOR) AND SPECIFIC GENE-EXPRESSION IN T-LYMPHOCYTES

Although prolactin and interleukin 2 (IL-2) can elicit distinct physio logical responses, we have found that their signal pathways share a co mmon signal transducer and activator of transcription, STAT5. STAT5 wa s originally identified as a mammary gland factor induced by prolactin in lactating breast cells. Here we demonstrate that STAT5 is activate d after IL-2 stimulation of two responsive lymphocyte cell lines, Nb2 and YT. Activation of STAT5 is measured both by IL-2-induced tyrosine phosphorylation and by IL-2-induced DNA binding. The STAT5 DNA recogni tion site is the same as the interferon gamma-activated site (GAS) in the interferon regulatory factor 1 gene. We demonstrate that the GAS e lement is necessary and sufficient for transcriptional induction by bo th IL-2 and prolactin in T lymphocytes. These results indicate that th e role of STAT5 in the regulation of gene expression is not restricted to mammary cells or to prolactin, but is an integral part of the sign al pathway of a critical immunomodulatory cytokine, IL-2.