Phosphatidic acid-mediated mitogenic activation of mTOR signaling

Y. Fang, M. Vilella-Bach, R. Bachmann, A. Flanigan, J. Chen

Research output: Contribution to journalArticlepeer-review

Abstract

The mammalian target of rapamycin (mTOR) governs cell growth and proliferation by mediating the mitogen- and nutrient-dependent signal transduction that regulates messenger RNA translation. We identified phosphatidic acid (PA) as a critical component of mTOR signaling. In our study, mitogenic stimulation of mammalian cells led to a phospholipase D-dependent accumulation of cellular PA, which was required for activation of mTOR downstream effectors. PA directly interacted with the domain in mTOR that is targeted by rapamycin, and this interaction was positively correlated with mTOR's ability to activate downstream effectors. The involvement of PA in mTOR signaling reveals an important function of this lipid in signal transduction and protein synthesis, as well as a direct [ink between mTOR and mitogens. Furthermore, these studies suggest a potential mechanism for the in vivo actions of the immunosuppressant rapamycin.

Original languageEnglish (US)
Pages (from-to)1942-1945
Number of pages4
JournalScience
Volume294
Issue number5548
DOIs
StatePublished - Nov 30 2001

ASJC Scopus subject areas

  • General

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