A Protein Tyrosine Kinase in the Interferon α/β Signaling Pathway.

The mutant human cell line 11,1 is unresponsive to interferon a. Here we describe the genetic complementatlon of this mutant and the Identification and cloning of the wild-type gene that corrects the defect. Using transtection with genomic DNA in conjunction with a powerful back-selection, we isolated a cosmid that reveils the mutant phenotype of 11,1 cells. The cosmid encodes a single message whose level is greatly reduced in mutant cells. Complementary DNA5 were cloned and found to be virtually Identical to tyk2, a humafl mRNA encoding a non-receptor protein tyrosine kinase of previously unknown function. This finding shows that fyk2 links the interferon α/β receptor to the cytoplasmic transcription factor that mediates activation of interferon-responsive genes. [ABSTRACT FROM AUTHOR]