STAT5 [MD311]

Membrane receptor signaling by various ligands, including interferons and growth hormones such as EGF, induces activation of JAK kinases which then leads to tyrosine phosphorylation of proteins that have been designated Stats (signal transducers and activators of transcription. STAT5A and STAT5B share 96% homology, undergo receptor tyrosine kinase or G protein-coupled receptor-dependent phosphorylation in response to cytokines or growth factors, and then form homo- or heterodimers that translocate to the nucleus, where they initiate transcription. Activation of Stat5a via IL-2, IL-3, IL-7 GM-CSF, erythropoietin, thrombopoietin and growth hormones influences proliferation, differentiation and apoptosis in lymphohematopoietic cells. Phosphorylation of STAT5A at Ser 127/Ser 128 and Ser 779 are contigent on ErbB4-mediated activation of STAT5A. Activation of STAT5B via IL-2, IL-4, CSF1 and growth hormones influences TCR signaling, apoptosis, adult mammary gland development and sexual dimorphism of liver gene expression. STAT5B is the major liver-expressed Stat5 form that has been shown to fuse with the retinoic acid receptor a gene in acute promyelocytic leukemias.