TYROSINE PHOSPHORYLATION AND ACTIVATION OF STAT5, STAT3, AND JANUS KINASES BY INTERLEUKIN-2 AND INTERLEUKIN-15

The cytokines interleukin 2 (IL-2) and IL-15 have similar biological e ffects on T cells and bind common hematopoietin receptor subunits. Pat hways that involve Janus kinases (JAKs) and signal transducers and act ivators of transcription (STATs) have been shown to be important for h ematopoietin receptor signaling. In this study we identify the STAT pr oteins activated by IL-2 and IL-15 in human T cells. IL-2 and IL-15 ra pidly induced the tyrosine phosphorylation of STAT3 and STAT5, and DNA -binding complexes containing STAT3 and STAT5 were rapidly activated b y these cytokines in T cells. IL 4 induced tyrosine phosphorylation an d activation of STAT3 but not STATS. JAK1 and JAK3 were tyrosine-phosp horylated in response to IL-2 and IL-15. Hence, the JAK and STAT molec ules that are activated in response to IL-2 and IL-15 are similar but differ from those induced by IL-4. These observations identify the STA T proteins activated by IL-2 and IL-15 and therefore define signaling pathways by which these T-cell growth factors may regulate gene transc ription.