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A protein tyrosine kinase in the interferon αβ signaling pathway

1992; Cell Press; Volume: 70; Issue: 2 Linguagem: Inglês

10.1016/0092-8674(92)90105-l

1097-4172

Laura Evelia Torres Velázquez, Marc Fellous, George R. Stark, Sandra Pellegrini,

Monoclonal and Polyclonal Antibodies Research

Abstract The mutant human cell line 11,1 is unresponsive to interferon α. Here we describe the genetic complementation of this mutant and the identification and cloning of the wild-type gene that corrects the defect. Using transfection with genomic DNA in conjunction with a powerful back-selection, we isolated a cosmid that reverts the mutant phenotype of 11,1 cells. The cosmid encodes a single message whose level is greatly reduced in mutant cells. Complementary DNAs were cloned and found to be virtually identical to tyk2 , a human mRNA encoding a non-receptor protein tyrosine kinase of previously unknown function. This finding shows that tyk2 links the interferon αβ receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes.