Stat3/Stat5 Signaling Antibody Sampler Kit #67088

Janus kinases (Jaks) and signal transducers and activators of transcription (Stats) are utilized by receptors for a wide variety of ligands including cytokines, hormones, growth factors, and neurotransmitters. Jaks, activated via autophosphorylation following ligand-induced receptor aggregation, phosphorylate tyrosine residues on associated receptors, Stat molecules, and other downstream signaling proteins (1,2). The phosphorylation of Stat proteins at conserved tyrosine residues activates SH2-mediated dimerization followed rapidly by nuclear translocation. Stat dimers bind to interferon response element (IRE) and gamma interferon-activated sequence (GAS) DNA elements, resulting in the transcriptional regulation of downstream genes (1,2). The remarkable range and specificity of responses regulated by the Stats is determined in part by the tissue-specific expression of different cytokine receptors, Jaks and Stats (2,3), and by the combinatorial coupling of various Stat members to different receptors. Serine phosphorylation in the carboxy-terminal transcriptional activation domain has been shown to regulate the function of Stat1, Stat2, Stat3, Stat4, and Stat5 (1). Phosphorylation of Stat3 at Ser727 via MAPK or mTOR pathways is required for optimal transcriptional activation in response to growth factors and cytokines including IFN-gamma and ciliary neurotrophic factor (CNTF) (4,5). Jak/Stat pathways also play important roles in oncogenesis, tumor progression, angiogenesis, cell motility, immune responses, and stem cell differentiation (6-11).

In the context of hematopoiesis, Stat3 and Stat5 may act antagonistically (12,13). Stat3 activity can promote differentiation of myeloid progenitor cells into neutrophils in a granulocyte colony-stimulating factor (G-CSF)-dependent manner, while Stat5 activation results in inhibition of this pathway in a granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent manner (13). Stat5 activity upregulates SOCS3, which subsequently inhibits Stat3 and results in differentiation to monocytes and macrophages (13). In addition to their roles in regulating gene expression as transcription factors, Stat3 and Stat5 are also capable of altering chromatin landscapes through recruitment of chromatin remodeling enzymes (14,15). While they serve many key functions in normal growth and development, if disrupted, the Jak2/Stat3 and Jak2/Stat5 signaling axes contribute to various diseases, including many types of cancer, non-alcoholic fatty liver disease, and eosinophilic cellulitis (16-20).