Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling

@article{Fang2001PhosphatidicAM,
  title={Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling},
  author={Yimin Fang and Montserrat Vilella-Bach and Rebecca A Bachmann and Asa Flanigan and Jie Chen},
  journal={Science},
  year={2001},
  volume={294},
  pages={1942 - 1945}
}
  • Yimin Fang, M. Vilella-Bach, +2 authors Jie Chen
  • Published 2001
  • Biology, Medicine
  • Science
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… Expand
Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway.
TLDR
The results demonstrate that leucine and PA signal through parallel pathways to activate mTORC1 and that PA mediates its effect through the ERK pathway, rather than through direct binding to mTOR. Expand
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  • J. Chen
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  • 2004
TLDR
A new picture of the rapamycin-sensitive signaling network is emerging, with implications in putative upstream regulators and additional downstream targets for mTOR. Expand
Phosphatidic acid and lipid-sensing by mTOR
  • D. A. Foster
  • Medicine, Chemistry
  • Trends in Endocrinology & Metabolism
  • 2013
TLDR
It is proposed that the responsiveness of mTOR/TOR to PA evolved as a means for sensing lipid precursors for membrane biosynthesis prior to doubling the mass of a cell and dividing. Expand
Negative regulation of mTOR activation by diacylglycerol kinases.
TLDR
It is demonstrated that diacylglycerol (DAG) and TCR engagement activate signaling in both mTOR complexes 1 and 2 through the activation of the Ras-mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (Mek1/2-Erk/12)-activator protein 1 (AP-1) pathway. Expand
Phospholipase D Mediates Nutrient Input to Mammalian Target of Rapamycin Complex 1 (mTORC1)*
TLDR
It is reported here that elevated PLD activity in human cancer cells is dependent on both amino acids and glucose and that amino acid- and glucose-induced increases in mTORC1 activity are dependent on PLD. Expand
Rapid mitogenic regulation of the mTORC1 inhibitor, DEPTOR, by phosphatidic acid.
TLDR
It is reported that DEPTOR is rapidly and temporarily dissociated from mTORC1 upon mitogenic stimulation, suggesting a mechanism underlying acute m TORC1 activation and providing a molecular explanation for the exquisite specificity of PA function. Expand
A novel pathway regulating the mammalian target of rapamycin (mTOR) signaling.
Originally discovered as an anti-fungal agent, the bacterial macrolide rapamycin is a potent immunosuppressant and a promising anti-cancer drug. In complex with its cellular receptor, theExpand
Regulation of mTOR by phosphatidic acid?
TLDR
The evidence implicating PLD and PA in the regulation of mTOR is summarized, and the implications of this novel and potentially important mechanism for regulating mTOR are discussed. Expand
Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells.
  • D. A. Foster
  • Biology, Medicine
  • Biochimica et biophysica acta
  • 2009
TLDR
The role of PA is summarized in regulating the mTOR-mediated signals that promote cancer cell survival and how PA impacts upon mTOR could be important for developing strategies to de-repress the survival signals that suppress apoptosis. Expand
TOR Signaling
TLDR
The history and recently discovered interacting partners and effectors of TOR, a protein at the center of the regulatory and signaling pathways that control cell growth and proliferation, are discussed. Expand
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