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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Schindler, C., Fu, X.-Y., Improta, T., Aebersold, R. & Darnell, J. E. Jr Proc. natn. Acad. Sci. U.S.A. 89, 7836–7839 (1992).
Fu, X.-Y., Schindler, C., Improta, T., Aebersold, R. & Darnell, J. E. Jr Proc. natn. Acad. Sci. U.S.A. 89, 7840–7843 (1992).
Schindler, C., Shuai, K., Prezioso, V. R. & Darnell, J. E. Jr Science 257, 809–813 (1992).
Shuai, K., Schindler, C., Prezioso, V. R. & Darnell, J. E. Jr Science 258, 1808–1812 (1992).
Velazquez, L., Fellows, M., Stark, G. R. & Pellegrini, S. Cell 70, 313–322 (1991).
Watling, D. et al. Nature 366, 166–170 (1993).
Wilks, A. F. et al. Molec. cell. Biol. 11, 2057–2065 (1991).
Shuai, K., Stark, G. R., Kerr, I. & Darnell, J. E. Jr Science 261, 1744–1746 (1993).
Hayes, T. E., Kitchen, A. M. & Cochran, B. H. Proc. natn. Acad. Sci. U.S.A. 84, 1272–1276 (1987).
Wagner, B. J., Hayes, T. E., Hoban, C. J. & Cochran, B. H. EMBO J. 9, 4477–4484 (1990).
Sadowski, H. B. & Gilman, M. Z. Nature 372, 79–82 (1993).
Decker, T., Lew, D. J., Mirkovitch, J. & Darnell, J. E. Jr EMBO J. 10, 927–932 (1991).
Pearse, R. N., Feinman, R., Shuai, K., Darnell, J. E. & Ravetch, J. V. Proc. natn. Acad. Sci. U.S.A. 90, 4314–4318 (1993).
Khan, K. D. et al. Proc. natn. Acad. Sci. U.S.A. 90, 6806–6810 (1993).
Kanno, Y. et al. Molec. cell. Biol. 13, 3951–3963 (1993).
Fu, X.-Y. Cell 70, 323–335 (1992).
Koch, C. A., Anderson, D., Moran, M. F., Ellis, C. & Pawson, T. Science 252, 668–674 (1991).
Waksman, G. et al. Nature 358, 646–653 (1992).
Overduin, M., Rios, C. B., Mayer, B. J., Baltimore, D. & Cowburn, D. Cell 70, 697–704 (1992).
McKendry, R. et al. Proc. natn. Acad. Sci. U.S.A. 88, 11455–11459 (1987).
Müller, M. et al. EMBO J. 12, 4221–4228 (1993).
Müller, M. et al. Nature 366, 129–135 (1993).
Pelligrini, S., John, J., Shearer, M., Kerr, I. M. & Stark, G. R. Molec. cell. Biol. 9, 4605–4612 (1989).
Howard, O. M. Z. et al. Oncogene 7, 895–900 (1992).
Witthuhn, B. A. et al. Cell 74, 227–236 (1993).
Silvennoinen, O. et al. Proc. natn. Acad. Sci. U.S.A. 90, 8429–8433 (1993).
Argetsinger, L. S. et al. Cell 74, 237–244 (1993).
Boyle, W. J., van der Geer, P. & Hunter, T. Meth. Enzym. 201, 110–149 (1991).
Kawasaki, E. in PRC Protocols: A Guide to Methods and Applications (eds M. Innis, D. Gelfand, J. Sinisky & T. White) 119 (Academic, San Diego, 1990).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/366580a0
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.