Interaction of IFNG with IFNGR

Stable Identifier
R-HSA-873926
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The IFNG receptor complex is a pre-assembled entity, as constitutive interactions are seen between IFNGR1 and IFNGR2, and between two IFNGR2 chains in the absence of ligand IFNG. JAK1 and JAK2 constitutively associate with the intracellular domains of the subunits of the IFNG receptor complex, providing it with tyrosine kinase activity. In unstimulated cells JAK1 preferentially associates with IFNGR1 and while JAK2 associates with IFNGR2 chains. JAK1 enhances the interaction between IFNGR1 and IFNGR2 chains, and thus has a major role in the pre-assembly of the IFNGR complex, in contrast the kinase activity of JAK2 is required to observe any signaling by IFNG.
IFNG binds directly to both the receptor chains IFNGR1 and IFNGR2. IFNGR1 is a high affinity receptor and binds directly to IFNG whereas IFNGR2 binds to IFNG in presence of IFNGR1. According to Krause et al. model IFNG binds to IFNGR1 chains first and then IFNGR2 chains interact with the IFNGR1:IFNG:IFNGR1 complex.

Literature References
PubMed ID Title Journal Year
10986460 Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex

Thiel, DJ, le Du, MH, Walter, RL, D'Arcy, A, Chene, C, Fountoulakis, M, Garotta, G, Winkler, FK, Ealick, SE

Structure 2000
7673114 Interaction between the components of the interferon gamma receptor complex

Kotenko, SV, Izotova, LS, Pollack, BP, Mariano, TM, Donnelly, RJ, Muthukumaran, G, Cook, JR, Garotta, G, Silvennoinen, O, Ihle, JN

J Biol Chem 1995
1396683 Stoichiometry of interaction between interferon gamma and its receptor

Fountoulakis, M, Zulauf, M, Lustig, A, Garotta, G

Eur J Biochem 1992
12438563 Seeing the light: preassembly and ligand-induced changes of the interferon gamma receptor complex in cells

Krause, CD, Mei, E, Xie, J, Jia, Y, Bopp, MA, Hochstrasser, RM, Pestka, S

Mol Cell Proteomics 2002
7615558 The Jak kinases differentially associate with the alpha and beta (accessory factor) chains of the interferon gamma receptor to form a functional receptor unit capable of activating STAT transcription factors

Sakatsume, M, Igarashi, K, Winestock, KD, Garotta, G, Larner, AC, Finbloom, DS

J Biol Chem 1995
16467876 Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains

Krause, CD, Lavnikova, N, Xie, J, Mei, E, Mirochnitchenko, OV, Jia, Y, Hochstrasser, RM, Pestka, S

Cell Res 2006
8550631 Identification of an interferon-gamma receptor alpha chain sequence required for JAK-1 binding

Kaplan, DH, Greenlund, AC, Tanner, JW, Shaw, AS, Schreiber, RD

J Biol Chem 1996
7617032 Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor

Walter, MR, Windsor, WT, Nagabhushan, TL, Lundell, DJ, Lunn, CA, Zauodny, PJ, Narula, SK

Nature 1995
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