Differential responsiveness of a splice variant of the human type I interferon receptor to interferons.
Chinese hamster ovary cells containing the yeast artificial chromosome F136C5 (alphaYAC) respond to all type I human interferons including IFN-alphaA, IFN-beta, and IFN-omega. The alphaYAC contains at least two genes encoding interferon-alpha receptor (IFN-alphaR) chains that are required for response to type I human interferons: Hu-IFN-alphaR1 and Hu-IFN-alphaR2. We previously isolated a splice variant of the Hu-IFN-alphaR1 chain designated Hu-IFN-alphaR1s. Chinese hamster ovary cells containing a disrupted alphaYAC, which contains a deletion in the human IFNAR1 gene, were transfected with expression vectors for the Hu-IFN-alphaR1 and Hu-IFN-alphaR1s chains. With these cells, two type I interferons have been identified which can interact with the splice variant (Hu-IFN-alphaR1s) and with the Hu-IFN-alphaR1 chains: Hu-IFN-alphaA and IFN-omega. Two other type I interferons, Hu-IFN-alphaB2 and Hu-IFN-alphaF, are capable of signaling through the Hu-IFN-alphaR1 chain only and cannot utilize the splice variant Hu-IFN-alphaR1s. Hu-IFN-alphaR1 and Hu-IFN-alphaR1s differ in that the latter is missing a single subdomain of the receptor extracellular domain encoded by exons 4 and 5 of the IFNAR1 gene. These results therefore indicate that different type I interferons require different subdomains of the Hu-IFN-alphaR1 receptor chain, and that the splice variant chain (Hu-IFN-alphaR1s) is functional.
Cook
J R
JR
Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
Cleary
C M
CM
Mariano
T M
TM
Izotova
L
L
Pestka
S
S
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D018244:Chromosomes, Artificial, Yeast; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D014644:Genetic Variation; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D006801:Humans; D006822:Hybrid Cells; D007370:Interferon Type I / Q000235:genetics / Q000494:pharmacology; D008969:Molecular Sequence Data; D012326:RNA Splicing; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000737:chemistry / Q000187:drug effects / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D015395:Histocompatibility Antigens Class I; D007370:Interferon Type I; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta