A Protein Tyrosine Kinase in the Interferon α/β Signaling Pathway (Reprinted from Cell, vol 70, pg 313-322, 1992)

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 conlunction 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.