Translocation of STAT1 dimer to nucleus Phoshorylation of STAT1 by JAK kinases Binding of STAT1 to p-IFNGR1 Release of STAT1 dimer from active receptor unit Phosphorylation of STAT1 at Ser727 Interaction of IFNG with IFNGR Phosphorylation of JAK2 Transphosphorylation of JAK1 Phosphorylation of IFNGR1 by JAK kinases GAF binds the GAS promoter elements in the IFNG-regulated genes Expression of IFNG-stimulated genes PathwayStep7063 PathwayStep7065 PathwayStep7064 PathwayStep7067 PathwayStep7066 PathwayStep7069 PathwayStep7068 PathwayStep7072 PathwayStep7071 PathwayStep7070 PathwayStep7073 PathwayStep7078 Interferon gamma signaling Authored: Garapati, P V, 2010-06-08 Edited: Garapati, P V, 2010-06-08 GENE ONTOLOGYGO:0060333 Interferon-gamma (IFN-gamma) belongs to the type II interferon family and is secreted by activated immune cells-primarily T and NK cells, but also B-cells and APC. INFG exerts its effect on cells by interacting with the specific IFN-gamma receptor (IFNGR). IFNGR consists of two chains, namely IFNGR1 (also known as the IFNGR alpha chain) and IFNGR2 (also known as the IFNGR beta chain). IFNGR1 is the ligand binding receptor and is required but not sufficient for signal transduction, whereas IFNGR2 do not bind IFNG independently but mainly plays a role in IFNG signaling and is generally the limiting factor in IFNG responsiveness. Both IFNGR chains lack intrinsic kinase/phosphatase activity and thus rely on other signaling proteins like Janus-activated kinase 1 (JAK1), JAK2 and Signal transducer and activator of transcription 1 (STAT-1) for signal transduction. IFNGR complex in its resting state is a preformed tetramer and upon IFNG association undergoes a conformational change. This conformational change induces the phosphorylation and activation of JAK1, JAK2, and STAT1 which in turn induces genes containing the gamma-interferon activation sequence (GAS) in the promoter. Pubmed14525967 Pubmed18929502 Pubmed9143700 Pubmed9462485 Reactome Database ID Release 43877300 Reactome, http://www.reactome.org ReactomeREACT_25078 Reviewed: Abdul-Sater, AA, Schindler, C, 2010-08-17 Regulation of IFNG signaling