How are Stat5 proteins activated by IL-2 family cytokines?
In addition to prolactin, Stat5 proteins are activated by a wide variety of cytokines and growth factors, including IL-2, IL-3, IL-5, IL-7, IL-9, IL-15, granulocyte-macrophage colony-stimulating factor, erythropoietin, growth hormone, thrombopoietin, epidermal growth factor and platelet-derived growth factor. The docking sites on a particular receptor seem to determine the specificity as to which STAT is activated by a cytokine. This has been clearly demonstrated for IL-2 family cytokines by eletrophoretic mobility shift assays (EMSA) using the peptides spanning the putative docking sites as competitive blockers of STAT dimerization (Demoulin et al., 1996; Lin et al., 1995). For example, only phosphorylated (but not non-phosphorylated) peptides spanning either Tyr-392 or Tyr-510 of IL-2R can efficiently compete with IL-2-induced Stat5 DNA binding to a GAS motif (Lin et al., 1995), but they cannot compete with the IL-4-induced Stat6 DNA binding activity. This indicates the specificity o
