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. 1992 Jul 24;70(2):313-22.
doi: 10.1016/0092-8674(92)90105-l.

A protein tyrosine kinase in the interferon alpha/beta signaling pathway

L Velazquez  1 , M Fellous, G R Stark, S Pellegrini
Affiliations

A protein tyrosine kinase in the interferon alpha/beta signaling pathway

L Velazquez et al. Cell. .

Abstract

The mutant human cell line 11.1 is unresponsive to interferon alpha. 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 alpha/beta receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes.

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