Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase (original) (raw)
- Letter
- Published: 02 July 1992
- Jongkyeong Chung1,2,
- David F. Fiorentino1,
- W. Michael Flanagan1,
- John Blenis1,2 &
- …
- Gerald R. Crabtree1
Nature volume 358, pages 70–73 (1992)Cite this article
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Abstract
THE macrolide rapamycin induces cell cycle Gl arrest in yeast and in mammalian cells1–3, which suggests that an evolutionarily conserved, rapamycin-sensitive pathway may regulate entry into S phase. In mammals, rapamycin inhibits interleukin-2 receptor-induced S phase entry and subsequent T-cell proliferation4–6, resulting in immunosuppression. Here we show that interleukin-2 selectively stimulates the phosphor) lation and activation of p70 S6 kinase but not the _erk_-encoded MAP kinases and _rsk_-encoded S6 kinases7,8. Rapamycin completely and rapidly inhibits interleukin-2-induced phosphorylation and activation of p70 S6 kinase at concentrations comparable to those blocking S phase entry of T cells (0.05–0.2 nM). The structurally related macrolide FK506 competitively antagonizes the actions of rapamycin, indicating that these effects are mediated by FKBP, which binds the transition-state mimic structure common to both rapamycin and FK506 (refs 4, 6, 9–11). The selective blockade of the p70 S6 kinase activation cascade by the rapamycin–FKBP complex implicates this signalling pathway in the regulation of T cell entry into S phase.
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Authors and Affiliations
- Howard Hughes Medical Institute, Unit in Molecular and Genetic Medicine, Beckman Center, Stanford University School of Medicine, Stanford, California, 94305-5425, USA
Calvin J. Kuo, Jongkyeong Chung, David F. Fiorentino, W. Michael Flanagan, John Blenis & Gerald R. Crabtree - Department of Cellular and Molecular Physiology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts, 02115, USA
Jongkyeong Chung & John Blenis
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- Calvin J. Kuo
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Kuo, C., Chung, J., Fiorentino, D. et al. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase.Nature 358, 70–73 (1992). https://doi.org/10.1038/358070a0
- Received: 26 February 1992
- Accepted: 29 May 1992
- Issue Date: 02 July 1992
- DOI: https://doi.org/10.1038/358070a0