Interaction between the components of the interferon gamma receptor complex.
Interferon gamma (IFN-gamma) signals through a multimeric receptor complex consisting of two different chains: the IFN-gamma receptor binding subunit (IFN-gamma R, IFN-gamma R1), and a transmembrane accessory factor (AF-1, IFN-gamma R2) necessary for signal transduction. Using cell lines expressing different cloned components of the IFN-gamma receptor complex, we examined the function of the receptor components in signal transduction upon IFN-gamma treatment. A specific IFN-gamma R2:IFN-gamma cross-linked complex was observed in cells expressing both IFN-gamma R1 and IFN-gamma R2 indicating that IFN-gamma R2 (AF-1) interacts with IFN-gamma and is closely associated with IFN-gamma R1. We show that the intracellular domain of IFN-gamma R2 is necessary for signaling. Cells coexpressing IFN-gamma R1 and truncated IFN-gamma R2, lacking the COOH-terminal 51 amino acids (residues 286-337), or cells expressing IFN-gamma R1 alone were unresponsive to IFN-gamma treatment as measured by MHC class I antigen induction. Jak1, Jak2, and Stat1 alpha were activated, and IFN-gamma R1 was phosphorylated only in cells expressing both IFN-gamma R1 and IFN-gamma R2. Jak2 kinase was shown to associate with the intracellular domain of the IFN-gamma R2.
Kotenko
S V
SV
Human Genome Sciences, Rockville, Maryland 20850-3338, USA.
Izotova
L S
LS
Pollack
B P
BP
Mariano
T M
TM
Donnelly
R J
RJ
Muthukumaran
G
G
Cook
J R
JR
Garotta
G
G
Silvennoinen
O
O
Ihle
J N
JN
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010766:Phosphorylation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D017471:Receptors, Interferon / Q000737:chemistry / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D000096743:Interferon gamma Receptor
D004268:DNA-Binding Proteins; D053613:Janus Kinase 1; D053614:Janus Kinase 2; D009838:Oligodeoxyribonucleotides; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; D015534:Trans-Activators; D000096743:Interferon gamma Receptor; C494079:STAT1 protein, human; C507904:JAK1 protein, human; C507924:JAK2 protein, human