Interaction of the transcriptional activator Stat-2 with the type I interferon receptor.
Binding of interferon-alpha (IFN alpha) to the multisubunit type I IFN receptor (IFNR) induces activation of the Tyk-2 and Jak-1 kinases and tyrosine phosphorylation of multiple signaling elements, including the Stat proteins that form the ISGF3 alpha complex. Although Jak kinases are required for IFN alpha-dependent activation of Stats, the mechanisms by which Stats interact with these kinases are not known. We report that Stat-2 associates with beta s subunit of the type I IFN receptor in an interferon-dependent manner. This association is rapid, occurring within 1 min of interferon treatment of cells, and is inducible by various type I (alpha, beta, omega) but not type II (gamma) IFNs. The kinetics of Stat-2-IFNR association are similar to the kinetics of phosphorylation of Stat-2, suggesting that during its binding to the type I IFNR, Stat 2 acts as a substrate for interferon-dependent tyrosine kinase activity. These findings support the hypothesis that the type I IFNR acts as an adaptor, linking Stat proteins to Jak kinases. Interaction of Stat-2 with the beta s subunit of the type I IFNR may be a critical signaling event, required for the formation of the ISGF3 alpha complex and downstream transcription of interferon-stimulated genes.
Uddin
S
S
Department of Medicine, Loyola University Chicago, Maywood, Illinois 60153, USA.
Chamdin
A
A
Platanias
L C
LC
D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D016898:Interferon-alpha / Q000494:pharmacology; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017471:Receptors, Interferon / Q000378:metabolism*; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D016898:Interferon-alpha; D017471:Receptors, Interferon; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; D015534:Trans-Activators