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Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins

Nature volume 366, pages 580–583 (1993)Cite this article

Abstract

BINDING of interferons IFN-α and IFN-γ to their cell surface receptors promptly induces tyrosine phosphorylation of latent cytoplasmic transcriptional activators1–4 (or Stat proteins, for signal transducers and activators of transcription). Interferon-α activates both Stat91 (Mr 91,000; ref. 1) and Statll3 (Mr 113,000; ref. 2) whereas IFN-γ activates only Stat91 (refs 3, 4). The activated proteins then move into the nucleus and directly activate genes induced by IFN-α and IFN-γ. Somatic cell genetics experiments have demonstrated a requirement for tyrosine kinase-2 (Tyk2) in the IFN-α response pathway5 and for Jak2 (ref. 6), a kinase with similar sequence7, in the IFN-γ response pathway. Here we investigate the tyrosine phosphorylation events on Stat and Jak proteins after treatment of cells with IFNs α and γ and with epidermal growth factor (EGF). Stat91 is phosphorylated on Tyr 701 after cells are treated with IFN-α and EGF, as it was after treatment with IFN-γ (ref. 8). We find that Jakl also becomes phosphorylated on tyrosine after cells are treated with these same three ligands, although each ligand is shown to activate at least one other differ-ent kinase. Jakl may therefore be the enzyme that phosphorylates Tyr701inStat91.

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Authors and Affiliations

  1. Laboratory of Molecular Cell Biology, The Rockefeller University, 1230 York Avenue, New York, 10021–6399, USA

    Ke Shuai & James E. Darnell

  2. Institute for Clinical and Experimental Cancer Research, University of Berne, Tiefenaustrasse 120, 3004, Berne, Switzerland

    Andrew Ziemiecki

  3. Ludwig Institute for Cancer Research, Royal Melbourne Hospital, Victoria, 3050, Australia

    Andrew F. Wilks & Ailsa G. Harpur

  4. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, 11724, USA

    Henry B. Sadowski & Michael Z. Gilman

Authors
  1. Ke Shuai
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  7. James E. Darnell
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Shuai, K., Ziemiecki, A., Wilks, A. et al. Polypeptide signalling to the nucleus through tyrosine phosphorylation of Jak and Stat proteins. Nature 366, 580–583 (1993). https://doi.org/10.1038/366580a0

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