PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase (original) (raw)
- Letter
- Published: 07 July 1994
- Timothy C. Grammar1,
- Katherine P. Lemon1,
- Andrius Kazlauskas1 na1 &
- …
- John Blenis1
Nature volume 370, pages 71–75 (1994)Cite this article
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Abstract
PLATELET-DERIVED growth factor receptor (PDGF-R) phosphory-lation at tyrosines 740/751 and insulin receptor phosphorylation of insulin receptor substrate-1 effects the recruitment and activation of phosphatidylinositol-3-OH kinase (PIK)1–5. Changes in PI(3)K activity correlate with cell growth but its downstream signal transducers are unknown4,5. Activation of the 70/85K S6 kinases (pp70S6k) by serine phosphorylation6,7 results in 40S ribosomal protein S6 phosphorylation and is important for Gl cell-cycle transition in a variety of cells8–11. Although receptor tyrosine kinases activate the microtubule-associated protein kinase cascade through SH2-/SH3-adaptor proteins, Sos and c-Ras12, it is unclear how tyrosine kinases are coupled to the pp70S6k phosphorylation cascade. Here we report that PI(3)K mediates PDGF or insulin receptor signalling to pp70S6k. PI(3)K-mediated activation of pp70S6k is independent of conventional protein kinase C isoforms. Additionally, rapamycin blocks pp70S6k activation by all mitogens8–10, without inhibiting PI(3)K, and acts downstream in this signalling system.
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Author notes
- Andrius Kazlauskas: National Jewish Center for Immunology and Respiratory Medicine, 1400 Jackson Street, Denver, Colorado 80206, USA
Authors and Affiliations
- Department of Cell Biology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts, 02115, USA
Jongkyeong Chung, Timothy C. Grammar, Katherine P. Lemon, Andrius Kazlauskas & John Blenis
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- Jongkyeong Chung
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Chung, J., Grammar, T., Lemon, K. et al. PDGF- and insulin-dependent pp70S6k activation mediated by phosphatidylinositol-3-OH kinase.Nature 370, 71–75 (1994). https://doi.org/10.1038/370071a0
- Received: 27 January 1994
- Accepted: 26 May 1994
- Issue Date: 07 July 1994
- DOI: https://doi.org/10.1038/370071a0