The Proximal Tyrosines of the Cytoplasmic Domain of the β Chain of the Type I Interferon Receptor Are Essential for Signal Transducer and Activator of Transcription (Stat) 2 Activation
The precise role of the different subunits (α/IFNAR1 and β L /IFNAR2) of the type I interferon receptor (IFN-R) in the activation of signal transducer and activator of transcription (Stat) 1, Stat2, and Stat3 has not yet been established. In this report we demonstrate that there are functionally r...
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Published in | The Journal of biological chemistry Vol. 274; no. 7; p. 4045 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
American Society for Biochemistry and Molecular Biology
12.02.1999
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Online Access | Get full text |
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Summary: | The precise role of the different subunits (α/IFNAR1 and β L /IFNAR2) of the type I interferon receptor (IFN-R) in the activation of signal transducer and activator of transcription (Stat)
1, Stat2, and Stat3 has not yet been established. In this report we demonstrate that there are functionally redundant phosphotyrosine-dependent
and -independent binding sites for Stat2 in the α and β subunits of the type I IFN-R. Expression of a type I IFN-R containing
only the constitutive Stat2 site or the proximal tyrosines of β L , but not the docking site on the α chain (Tyr 466 and Tyr 481 ), supported low levels of Stat2 activation. However, the presence of only one intact Stat2 site did not lead to induction
of interferon-stimulated gene factor 3 (ISGF3) or an antiviral state. Normal levels of Stat2 tyrosine phosphorylation, induction
of ISGF3, and an antiviral effect always required the proximal tyrosines of β L and at least one of the other Stat2 sites (Tyr α466,â481 or β L404â462 ). These data suggest that a threshold of Stat2 tyrosine phosphorylation is required for complete activation of ISGF3. Interestingly,
a receptor in which all tyrosines were mutated to phenylalanine shows normal Stat3 phosphorylation and low levels of activation
of Stat1. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1074/jbc.274.7.4045 |