Figure 2.

JAK-STAT signaling pathway. When a ligand (usually a cytokine) binds to its receptor in a cell, it triggers the autophosphorylation of the receptor-associated Janus kinases (JAKs). Activated JAKs phosphorylate the intracellular tail of the receptor on critical tyrosine residues, which leads to the recruitment and binding of signal transducer and activator of transcription (STAT) proteins. STATs are phosphorylated by JAKs, which induces their dissociation from the receptor. STATs form homo- or heterodimers and translocate into the cell nucleus, where they bind to specific DNA regions and activate target gene expression. Negative regulators of the JAK-STAT signaling pathway include protein tyrosine phosphatases (PTPs), which remove phosphate groups from receptors, JAKs and STATs; protein inhibitor of activated STAT (PIAS), that prevent the DNA-binding activity of STATs; and suppressor of cytokine signaling proteins (SOCS), which inhibit the activity of JAKs. DNA, deoxyribonucleic acid; JAK, Janus kinase; P, phosphate; PIAS, protein inhibitor of activated STAT; PTP, protein tyrosine phosphatase; SOCS, suppressor of cytokine signaling proteins; STAT, signal transducer and activator of transcription.