Phosphatidic acid-mediated mitogenic activation of mTOR signaling

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

Research output: Contribution to journalArticle

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

Fingerprint

Phosphatidic Acids
Sirolimus
Mitogens
Signal Transduction
Phospholipase D
Ink
Immunosuppressive Agents
Cell Proliferation
Lipids
Food
Messenger RNA
Growth

ASJC Scopus subject areas

  • General

Cite this

Fang, Y., Vilella-Bach, M., Bachmann, R., Flanigan, A., & Chen, J. (2001). Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science, 294(5548), 1942-1945. https://doi.org/10.1126/science.1066015

Phosphatidic acid-mediated mitogenic activation of mTOR signaling. / Fang, Y.; Vilella-Bach, M.; Bachmann, R.; Flanigan, A.; Chen, J.

In: Science, Vol. 294, No. 5548, 30.11.2001, p. 1942-1945.

Research output: Contribution to journalArticle

Fang, Y, Vilella-Bach, M, Bachmann, R, Flanigan, A & Chen, J 2001, 'Phosphatidic acid-mediated mitogenic activation of mTOR signaling', Science, vol. 294, no. 5548, pp. 1942-1945. https://doi.org/10.1126/science.1066015
Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J. Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science. 2001 Nov 30;294(5548):1942-1945. https://doi.org/10.1126/science.1066015
Fang, Y. ; Vilella-Bach, M. ; Bachmann, R. ; Flanigan, A. ; Chen, J. / Phosphatidic acid-mediated mitogenic activation of mTOR signaling. In: Science. 2001 ; Vol. 294, No. 5548. pp. 1942-1945.
@article{2ca15ec22871422eb6e96df2dbba7a06,
title = "Phosphatidic acid-mediated mitogenic activation of mTOR signaling",
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.",
author = "Y. Fang and M. Vilella-Bach and R. Bachmann and A. Flanigan and J. Chen",
year = "2001",
month = "11",
day = "30",
doi = "10.1126/science.1066015",
language = "English (US)",
volume = "294",
pages = "1942--1945",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5548",

}

TY - JOUR

T1 - Phosphatidic acid-mediated mitogenic activation of mTOR signaling

AU - Fang, Y.

AU - Vilella-Bach, M.

AU - Bachmann, R.

AU - Flanigan, A.

AU - Chen, J.

PY - 2001/11/30

Y1 - 2001/11/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035976615&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035976615&partnerID=8YFLogxK

U2 - 10.1126/science.1066015

DO - 10.1126/science.1066015

M3 - Article

C2 - 11729323

AN - SCOPUS:0035976615

VL - 294

SP - 1942

EP - 1945

JO - Science

JF - Science

SN - 0036-8075

IS - 5548

ER -