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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Cloning, Molecular
  • Cosmids
  • DNA
  • Gene Expression Regulation*
  • Humans
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / isolation & purification
  • RNA, Messenger / analysis
  • Receptors, Immunologic
  • Receptors, Interferon
  • Sequence Alignment
  • Signal Transduction / genetics*
  • Transcription Factors / chemistry


  • RNA, Messenger
  • Receptors, Immunologic
  • Receptors, Interferon
  • Transcription Factors
  • DNA
  • Protein-Tyrosine Kinases

Associated data

  • GENBANK/X54637