描述:
The Stat proteins function both as cytoplasmic signal transducers and as activators of transcription. Seven mammalian STATs have been
identified: Stat 1-4, Stat5a, 5b, and Stat6. The SH3 domain of Stat5 shows extensive homology with the SH2 domains of Stat1 and Stat2. This
homology leads to speculation that it may have a broader physiological role than originally anticipated and has led to its classification as a
member of the Stat family. Stat5 has been further characterized and shown to be encoded by two separate genes, Stat5a and Stat5b that share
over 90% identity at the amino acid level. Further insight into the exact biological role of Stat5a and Stat5b was determined with the
generation of Stat5a and Stat5b deficient mice. Stat5a was shown to be involved in lactogenesis and mammary development, while Stat5b was
shown to be involved in growth hormone signaling and to play a role in liver gene expression. Both Stat5a and Stat5b share similarities, both
are involved in IL-2 induced peripheral T cell proliferation. Stat5 (MGF) mRNA expression is highest in mammary gland tissue. Lower levels
are found in ovary, thymus, spleen, kidney, lung, muscle, and the adrenal gland. The peptide hormone, prolactin, binds to the prolactin
receptor (PRLR) to initiate the lactogenic response. There are at least three forms of PRLR; however, only the long form is able to activate the
92 kDa Stat5 protein by inducing phosphorylation at Tyr694. Once phosphorylated, Stat5 becomes an essential transcription factor which
binds to the β-casein gene promoter. Stat5 activity is tightly regulated throughout gestation, lactation, and post-lactation. Treatment of
activated Stat5 with a protein tyrosine phosphatase results in the loss of DNA binding activity. The presence of an SH2 domain within Stat5
suggests that it may directly interact with protein tyrosine kinases (PTKs) such as JAK2.