STAT protein

Much research has focused on elucidating the roles each of these domains play in regulating different STAT isoforms.

Extracellular binding of cytokines or growth factors induce activation of receptor-associated Janus kinases, which phosphorylate a specific tyrosine residue within the STAT protein promoting dimerization via their SH2 domains.

Originally, STAT proteins were described as latent cytoplasmic transcription factors as phosphorylation was thought to be required for nuclear retention.

However, unphosphorylated STAT proteins also shuttle between the cytosol and nucleus, and play a role in gene expression.

Once STAT reaches the nucleus, it binds to a consensus DNA-recognition motif called gamma-activated sites (GAS) in the promoter region of cytokine-inducible genes and activates transcription.