Members of the STAT (signal transducer and activators of transcription) family are important intracellular messengers of cytokines and growth factor signaling. Seven mammalian STATs have been identified: STAT1-4, 5a, 5b, and 6. STAT proteins are activated by tyrosine phosphorylation, which causes dimerization and translocation to the nucleus, where the STAT dimer acts as a transcription factor. STAT5a and STAT5b are encoded by 2 separate genes but 90% homologous at the amino acid level. JAK-mediated phosphorylation of Tyr694 on STAT5a/b occurs in response to many cytokines and growth factors including interferon-alpha, GM-CSF, IL-2, and IL-3. Non-JAK-mediated activation of STAT5 (i.e., by BCR-ABL in certain leukemias) has also been reported. Activated STAT5 promotes transcription of genes that mediate cell growth and survival.
