Signal transducers and activators of transcription (STATs) is a group of transcription factors. They play a critical role in diverse signal transduction pathways that govern cellular survival, proliferation, differentiation and apoptosis. They mediate signaling from a number of membrane receptors that include interferon, interleukin (IL-2), hematopoietic and growth factors receptors (GM-CSF, growth hormone and prolactin). Stat5 signals can be detected in GM-CSF stimulated monocytes as opposed to non activated control samples. Phosphorylation at Tyr694 is obligatory for Stat5 activation. STAT protein activation may be mediated by members of both JAK and Src family members following cytokine/growth factor stimulation. JAK kinases appear to be essential for the phosphorylation of the cytokine receptors which results in the creation of docking sites on the receptors for binding of SH2- containing proteins such as STATs, Src-kinases and other signaling intermediates. The integration of these diverse signaling cues from active JAK kinases, members of the Src-family kinases and STAT proteins, leads to cell proliferation, cell survival and differentiation, the end-point of the cytokine/growth factor stimulus. STAT protein activation has been observed in diverse cell types. Constitutive STAT activation has been detected in a wide variety of human primary tumor specimens and tumor cell lines. Stat5 is constitutively active in some leukemic cell types. Phosphorylated Stat5 is found in some endothelial cells treated with IL-3, which suggests its involvement in angiogenesis and cell motility.
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