STAT3 Pathway

Signal Transducers and Activators of Transcription (STATs) are a family of cytoplasmic proteins with Src Homology-2 (SH2) domains that act as signal messengers and transcription factors and participate in normal cellular responses to Cytokines and Growth Factors. STATs are activated via the tyrosine phosphorylation cascade after ligand binding and stimulation of the Cytokine Receptor-Kinase complex and Growth Factor-Receptor complex e.g., the Epidermal Growth Factor (EGF) or Fibroblast Growth Factor (FGF). Ligands that signal through the same class of receptor complexes usually activate the same set of STAT factors, e.g. all IL-6-type cytokines activate STAT3 and STAT1. STAT3, is a transcription factor which in humans is encoded by the STAT3 gene.Stat3 in the cytoplasm of unstimulated cells becomes activated by recruitment to phosphotyrosine motifs within complexes of growth factor receptors , cytokine receptors, or non-receptor tyrosine kinases (e.g., Src and BCR-ABL) through their SH2 domain. Stat3 is then phosphorylated on a tyrosine residue by activated tyrosine kinases in receptor complexes. Phosphorylated Stat3 forms homodimers and heterodimers and translocates to the nucleus. In the nucleus, Stat3 dimers bind to specific promoter elements of target genes and regulate gene expression. The Stat3 signaling pathway plays an important role in normal development, particularly hematopoiesis, and regulates cancer metastasis by regulating the expression of genes that are critical to cell survival, cell proliferation, invasion, angiogenesis, and tumor immune evasion.