Signal transducer and activator of transcription protein (STAT protein) (STAT)

The Signal transducer and activator of transcription proteins (STAT proteins) constitute a family of intracellular transcription factors that mediate critical aspects of cellular immunity, proliferation, apoptosis, and differentiation. There are seven mammalian members—STAT1, STAT2, STAT3, STAT4, STAT5A/B, and STAT6—all sharing a conserved structure with domains for dimerization (N-terminal and SH2), nuclear localization (coiled-coil), DNA binding (DNA-binding domain), and transcriptional activation (C-terminal domain). Activation occurs when cytokines or growth factors bind to their receptors on the cell surface. This triggers associated Janus kinases to phosphorylate specific tyrosine residues on the receptor as well as on the cytoplasmic tail of nearby STAT proteins. Phosphorylated STATs dimerize via their SH2 domains and then translocate into the nucleus where they bind specific DNA motifs to regulate gene expression. Unphosphorylated forms can also shuttle between cytoplasm and nucleus with regulatory functions still being elucidated. The JAK/STAT pathway is central to many biological processes including hematopoiesis; immune cell maturation; inflammation regulation; bone development; cellular growth control; migration; survival/apoptosis decisions; allergic responses; among others. Dysregulation or mutation—especially gain-of-function mutations—of certain family members like STAT3 is implicated in various cancers as well as autoimmune diseases due to unchecked cell proliferation or impaired apoptosis.

Other names

STAT proteinSignal transducer and activator of transcriptionSTAT family memberJAK/STAT pathway component

Generally involves inhibition of phosphorylation, dimerization, or DNA binding activity.