Identification of a domain in the beta subunit of the type I interferon (IFN) receptor that exhibits a negative regulatory effect in the growth inhibitory action of type I IFNs.
Expression of human alpha and long form of the beta (betaL) subunits of type I interferon receptor (IFN-R) in mouse cells is sufficient to activate the Jak-Stat pathway and to elicit an antiviral state in response to human IFNalpha2 and IFNbeta. We demonstrate herein, however, that these cells respond to the antiproliferative effects of murine IFNalphabeta but not human type I IFNs. These results suggest that an unknown species-specific component is required for the antiproliferative effect of human type I IFNs. The absence of this component can be complemented by expressing the human betaL chain truncated at amino acid 346. Thus, the distal region of betaL appears to function as a negative regulator of the growth inhibitory effects of type I IFNs. Further studies looking for possible targets of the betaL regulatory domain demonstrated that this region associates with a tyrosine phosphatase. These results suggest that a protein associated with the negative regulatory domain of betaL, likely a tyrosine phosphatase, plays a role in regulating the growth inhibitory effects of human type I IFNs.
Platanias
L C
LC
Section of Hematology/Oncology, University of Illinois at Chicago, and West Side Veterans Affairs Hospital, Chicago, Illinois 60607, USA.
Domanski
P
P
Nadeau
O W
OW
Yi
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T
Uddin
S
S
Fish
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Neel
B G
BG
Colamonici
O R
OR
D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D016898:Interferon-alpha / Q000494:pharmacology; D053613:Janus Kinase 1; D051379:Mice; D016296:Mutagenesis / Q000235:genetics; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017471:Receptors, Interferon / Q000737:chemistry* / Q000502:physiology; D017384:Sequence Deletion / Q000235:genetics
D007370:Interferon Type I; D016898:Interferon-alpha; D017471:Receptors, Interferon; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; D017027:Protein Tyrosine Phosphatases