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Phosphatidic acid-mediated mitogenic activation of mTOR signaling

Y Fang1, M Vilella-Bach, R Bachmann

  • 1Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA.

Science (New York, N.Y.)
|December 1, 2001
PubMed

Insights

Phosphatidic acid (PA) is crucial for mammalian target of rapamycin (mTOR) signaling, controlling cell growth and protein synthesis. This lipid directly interacts with mTOR, linking mitogens to cell growth and explaining rapamycin

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Biochemistry

Background:

  • The mammalian target of rapamycin (mTOR) pathway regulates fundamental cellular processes like growth, proliferation, and protein synthesis.
  • mTOR integrates signals from mitogens and nutrients to control downstream cellular activities, including messenger RNA translation.

Purpose of the Study:

  • To identify critical components involved in mammalian target of rapamycin (mTOR) signaling.
  • To elucidate the role of phosphatidic acid (PA) in the activation and regulation of mTOR.
  • To explore the mechanistic link between mitogenic stimulation, PA, and mTOR activity.

Main Methods:

  • Investigated mitogenic stimulation in mammalian cells.
  • Measured cellular phosphatidic acid (PA) accumulation dependent on phospholipase D.
  • Assessed the interaction between PA and the rapamycin-binding domain of mTOR.
  • Evaluated the impact of PA on mTOR's activation of downstream effectors.

Main Results:

  • Mitogenic stimulation induced a phospholipase D-dependent increase in cellular phosphatidic acid (PA).
  • Accumulated PA was essential for activating mTOR's downstream signaling pathways.
  • Phosphatidic acid (PA) directly bound to the rapamycin-sensitive domain of mTOR, correlating with downstream activation.

Conclusions:

  • Phosphatidic acid (PA) is a key lipid mediator in mammalian target of rapamycin (mTOR) signaling.
  • PA links mitogenic signals to mTOR activation, influencing protein synthesis and cell growth.
  • The findings suggest a mechanism for the action of the immunosuppressant rapamycin via PA-mTOR interaction.

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