fig1

Figure 1. JAK/STAT pathway involving receptors lacking intrinsic tyrosine kinase activity: Upon ligand binding, transmembrane cytokine receptors multimerize, bringing receptor-associated JAKs into close physical proximity. Once activated via transphosphorylation, JAKs phosphorylate the cytoplasmic domain of the receptor to provide a docking site for STAT. The bound STATs are then phosphorylated and activated by JAKs. Activated STATs dimerize and translocate into the nucleus where act as transcription factors. Suppressors of cytokine signaling (SOCS) family of proteins inhibit JAK activation; cytokine-inducible SH2-containing protein (CIS) blocks the STAT docking site on the receptor; Protein inhibitor of activated STAT (PIAS) proteins inhibit STAT binding to promoter regions of target genes; and protein tyrosine phosphatase receptors (PTPRs) dephosphorylate STATs. JAKs: Janus kinases; STAT: signal transducer and activator of transcription