STAT5A AND STAT5B PROTEINS HAVE ESSENTIAL AND NONESSENTIAL, OR REDUNDANT, ROLES IN CYTOKINE RESPONSES

A variety of cytokines mediate the activation of Janus protein tyrosin e kinases (Jaks). The Jaks then phosphorylate cellular substrates, inc luding members of the signal transducers and activators of transcripti on (Stat) family of transcription factors. Among the Stats, the two hi ghly related proteins, Stat5a and Stat5b, are activated by a variety o f cytokines. To assess the role of the Stat5 proteins, mutant mice wer e derived that have the genes deleted individually or together. The ph enotypes of the mice demonstrate an essential, and often redundant, ro le for the two Stat5 proteins in a spectrum of physiological responses associated with growth hormone and prolactin. Conversely, the respons es to a variety of cytokines that activate the Stat5 proteins, includi ng erythropoietin, are largely unaffected.