title: A protein tyrosine kinase in the interferon alpha/beta signaling pathway.
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.
authors.affiliation: Unité INSERM 276, Institut Pasteur, Paris, France.
authors.forename: L
authors.initials: L
authors.lastname: Velazquez
authors.forename: M
authors.initials: M
authors.lastname: Fellous
authors.forename: G R
authors.initials: GR
authors.lastname: Stark
authors.forename: S
authors.initials: S
authors.lastname: Pellegrini
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D003360:Cosmids; D004247:DNA; D005786:Gene Expression Regulation; D006801:Humans; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000302:isolation & purification; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D016415:Sequence Alignment; D015398:Signal Transduction / Q000235:genetics*; D014157:Transcription Factors / Q000737:chemistry
chemical_list: D012333:RNA, Messenger; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D014157:Transcription Factors; D004247:DNA; D011505:Protein-Tyrosine Kinases