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.
Krause
Christopher D
CD
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.
Lavnikova
Natasha
N
Xie
Junxia
J
Mei
Erwen
E
Mirochnitchenko
Olga V
OV
Jia
Yiwei
Y
Hochstrasser
Robin M
RM
Pestka
Sidney
S
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