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Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-& gamma; signal transduction pathway

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Abstract

INTERFERONS (IFNs) & alpha;/& beta; (type I) and & gamma; (type II) bind to distinct cell surface receptors1, inducing transcription of overlapping sets of genes by intracellular pathways that have recently attracted much attention2,3. Previous studies using cell lines selected for their inability to respond to IFN-& alpha; (ref. 4) have shown that the protein kinase Tyk2 plays a central role in the IFN & alpha;/& beta; response5. Here we report the isolation of the cell line & gamma;l A, selected for its inability to express IFN-& gamma;-inducible cell-surface markers, that is deficient in all aspects of the IFN-& gamma; response tested, but responds normally to IFNs & alpha; and & beta;. The mutant cells can be complemented by the expression of another member of the JAK family of protein tyro-sine kinases, JAK2 (refs 6& ndash;9). Unlike IFNs & alpha; and & beta;, IFN-& gamma; induces rapid tyrosine phosphorylation of JAK2 in wild-type cells, and JAK2 immunoprecipitates from these cells show tyrosine kinase activity. These responses are absent in & gamma;l A cells. JAK2 is therefore required for the response to IFN-& gamma; but not to IFNs & alpha; and & beta;.

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Author notes

  1. Olli Silvennoinen: Department of Pharmacology, New York University Medical Center, New York, New York 10016, USA

  2. Bruce A. Witthuhn, Frederick W. Quelle and James N. Ihle: Department of Biochemistry, St Jude Children's Research Hospital, 332 North Lauderdale, Memphis, Tennessee 38101-0318, USA

  3. Chris Schindler: Department of Molecular Medicine, Columbia University Medical Center, New York, New York 10032, USA

  4. George R. Stark: Department of Molecular Biology, Cleveland Clinic Foundation Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195-5001. USA

Authors and Affiliations

  1. Imperial Cancer Research Fund, 44 Lincoln's Inn Fields, London, WC2A 3PX, UK

    Diane Watling, Dmitry Guschin, Mathias Müller, Olli Silvennoinen, Bruce A. Witthuhn, Frederick W. Quelle, Neil C. Rogers, Chris Schindler, George R. Stark, James N. Ihle & lan M. Kerr

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  1. Diane Watling
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  2. Dmitry Guschin
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  3. Mathias Müller
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  4. Olli Silvennoinen
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  5. Bruce A. Witthuhn
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  6. Frederick W. Quelle
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  7. Neil C. Rogers
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  8. Chris Schindler
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  9. George R. Stark
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  10. James N. Ihle
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  11. lan M. Kerr
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Watling, D., Guschin, D., Müller, M. et al. Complementation by the protein tyrosine kinase JAK2 of a mutant cell line defective in the interferon-& gamma; signal transduction pathway. Nature 366, 166–170 (1993). https://doi.org/10.1038/366166a0

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