Preassembly and ligand-induced restructuring of the chains of the IFN-gamma receptor complex: the roles of Jak kinases, Stat1 and the receptor chains.
We previously demonstrated using noninvasive technologies that the interferon-gamma (IFN-gamma) receptor complex is preassembled (1). In this report we determined how the receptor complex is preassembled and how the ligand-mediated conformational changes occur. The interaction of Stat1 with IFN-gammaR1 results in a conformational change localized to IFN-gammaR1. Jak1 but not Jak2 is required for the two chains of the IFN-gamma receptor complex (IFN-gammaR1 and IFN-gammaR2) to interact; however, the presence of both Jak1 and Jak2 is required to see any ligand-dependant conformational change. Two IFN-gammaR2 chains interact through species-specific determinants in their extracellular domains. Finally, these determinants also participate in the interaction of IFN-gammaR2 with IFN-gammaR1. These results agree with a detailed model of the IFN-gamma receptor that requires the receptor chains to be pre-associated constitutively for the receptor to be active.
Department of Molecular Genetics, Microbiology and Immunology, The University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, 08854, USA.
Christopher D
CD
Krause
Natasha
N
Lavnikova
Junxia
J
Xie
Erwen
E
Mei
Olga V
OV
Mirochnitchenko
Yiwei
Y
Jia
Robin M
RM
Hochstrasser
Sidney
S
Pestka
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D011505:Protein-Tyrosine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D017471:Receptors, Interferon / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D050794:STAT1 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014162:Transfection; D000096743:Interferon gamma Receptor
D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008024:Ligands; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D000096743:Interferon gamma Receptor; C507904:JAK1 protein, human; C507924:JAK2 protein, human