The short form of the interferon alpha/beta receptor chain 2 acts as a dominant negative for type I interferon action.
We have characterized the functional properties of the short form of the human interferon alpha/beta receptor chain 2 (IFNAR2), denoted IFNAR2.1. IFNAR2.1 contains a shortened cytoplasmic domain when compared with the recently cloned full-length IFNAR2 chain (IFNAR2. 2). We show that IFNalpha8 and IFNbeta1b induce antiviral and antiproliferative activity in mouse cell transfectants expressing the human IFNAR1 chain of the receptor and induce the formation of STAT1/STAT2 dimers in IFN-stimulated response element (ISRE)-dependent gel shift assays. In contrast, coexpression of IFNAR2.1 with IFNAR1 reduces the IFN-induced antiviral, antiproliferative and ISRE-dependent gel shift binding activity conferred by IFNAR1 alone. No antiviral or antiproliferative response to IFN, nor IFN-induced ISRE-dependent gel shift binding activity, was observed when IFNAR2.1 was expressed alone in murine cells. Therefore, IFNAR2.1 acts as a dominant negative for these IFN-induced activities. Our results suggest that IFNAR2.1 represents a nonfunctional version of the full-length chain (IFNAR2.2).
Pfeffer
L M
LM
Department of Pathology, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. lpfeffer@utmem1.utmem.edu
Basu
L
L
Pfeffer
S R
SR
Yang
C H
CH
Murti
A
A
Russell-Harde
D
D
Croze
E
E
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D001665:Binding Sites; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha / Q000494:pharmacology; D016899:Interferon-beta / Q000494:pharmacology; D008565:Membrane Proteins; D051379:Mice; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004268:DNA-Binding Proteins; C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; C494227:IRF9 protein, human; C508032:Ifnar1 protein, mouse; C508034:Ifnar2 protein, mouse; D007370:Interferon Type I; D050832:Interferon-Stimulated Gene Factor 3; D050834:Interferon-Stimulated Gene Factor 3, gamma Subunit; D016898:Interferon-alpha; C494228:Isgf3g protein, mouse; D008565:Membrane Proteins; D017471:Receptors, Interferon; D014157:Transcription Factors; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta