STAT3 gene in JAK-STAT Pathway

STAT proteins were originally identified as inactive cytoplasmic transcription factors. The biological role of STAT proteins which regulate growth, survival, apoptosis, host defense, stress & differentiation in functions depending on the signaling pathway & the target tissue. STAT family consists of STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B & STAT6genes. 90kDa to 115kDa is the size STAT proteins. The STAT proteins in JAK-signal transducer and activator of transcription (JAK-STAT) signaling pathway. STATs are non- functional in the cytoplasm. After, the Ligand-induced activation of inactive cytoplasmic JAK kinases leads to tyrosine phosphorylation of inactive monomeric or N-domain-mediated dimeric STAT proteins, promoting the formation of active SH2- domain-mediated homodimers of STAT proteins. The tyrosine- phosphorylated STAT dimers are actively transported to the nucleus by using metabolic energy and the importin α/β and RanGDP complex. When the activated STAT dimers are present in the nucleus then they can bind to consensus DNA- recognition motifs, called gamma-activated sites (GAS), in the promoters of cytokine-inducible genes, resulting in transcriptional activation. STATs can bind DNA as dimers or as N-domain-mediated tetramers.