The interferon gamma (IFN-gamma) receptor: a paradigm for the multichain cytokine receptor

With the purification and cloning of the interferon gamma (IFN-gamma) receptor chains the mechanism of IFN-gamma action and the resultant signal transduction events were delineated in remarkable detail. The interferon gamma (IFN-gamma) receptor complex consists of two chains: IFN-gammaR1, the ligand-binding chain, and IFN-gammaR2, the accessory chain. Binding of IFN-gamma causes oligomerization of the two IFN-gamma Receptor subunits, IFN-gammaR1 and IFN-gammaR2, which initiates the signal transduction events: activation of JAK1 and JAK2 receptor associated Protein Tyrosine Kinases, phosphorylation of the IFN-gammaR1 intracellular domain on Tyr440 followed by phosphorylation and activation of Stat1alpha, the latent transcriptional factor. With all these steps established, the IFN-gamma Receptor complex has provided the basic model for understanding the receptors for other members of the family of class II Cytokine Receptors.