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Science 294 (5548): 1942-1945

Copyright © 2001 by the American Association for the Advancement of Science

Phosphatidic Acid-Mediated Mitogenic Activation of mTOR Signaling

Yimin Fang, Montserrat Vilella-Bach, Rebecca Bachmann, Asa Flanigan, Jie Chen*

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 link between mTOR and mitogens. Furthermore, these studies suggest a potential mechanism for the in vivo actions of the immunosuppressant rapamycin.

Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA.
*   To whom correspondence should be addressed. E-mail: jiechen{at}uiuc.edu



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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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R. Jaafar, C. Zeiller, L. Pirola, A. Di Grazia, F. Naro, H. Vidal, E. Lefai, and G. Nemoz (2011)
J. Biol. Chem. 286, 22609-22621
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Negative regulation of mTOR activation by diacylglycerol kinases.
B. K. Gorentla, C.-K. Wan, and X.-P. Zhong (2011)
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   Abstract »    Full Text »    PDF »
Molecular, cellular, and physiological responses to phosphatidic acid formation in plants.
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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L. Zhang, J. R. Ussher, T. Oka, V. J. J. Cadete, C. Wagg, and G. D. Lopaschuk (2011)
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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M. Lung, Y. V. Shulga, P. T. Ivanova, D. S. Myers, S. B. Milne, H. A. Brown, M. K. Topham, and R. M. Epand (2009)
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   Abstract »    Full Text »    PDF »
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A. K. Ghosh, N. Chauhan, S. Rajakumari, G. Daum, and R. Rajasekharan (2009)
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   Abstract »    Full Text »    PDF »
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T. Itoh, J. Hasegawa, K. Tsujita, Y. Kanaho, and T. Takenawa (2009)
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   Abstract »    Full Text »    PDF »
Enzymatic measurement of phosphatidic acid in cultured cells.
S.-y. Morita, K. Ueda, and S. Kitagawa (2009)
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   Abstract »    Full Text »    PDF »
Site-Specific mTOR Phosphorylation Promotes mTORC1-Mediated Signaling and Cell Growth.
H. A. Acosta-Jaquez, J. A. Keller, K. G. Foster, B. Ekim, G. A. Soliman, E. P. Feener, B. A. Ballif, and D. C. Fingar (2009)
Mol. Cell. Biol. 29, 4308-4324
   Abstract »    Full Text »    PDF »
The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions.
T. K. O'Neil, L. R. Duffy, J. W. Frey, and T. A. Hornberger (2009)
J. Physiol. 587, 3691-3701
   Abstract »    Full Text »    PDF »
Sequential Regulation of DOCK2 Dynamics by Two Phospholipids During Neutrophil Chemotaxis.
A. Nishikimi, H. Fukuhara, W. Su, T. Hongu, S. Takasuga, H. Mihara, Q. Cao, F. Sanematsu, M. Kanai, H. Hasegawa, et al. (2009)
Science 324, 384-387
   Abstract »    Full Text »    PDF »
Cellular mechanisms regulating protein synthesis and skeletal muscle hypertrophy in animals.
M. Miyazaki and K. A. Esser (2009)
J Appl Physiol 106, 1367-1373
   Abstract »    Full Text »    PDF »
Mitochondrial diacylglycerol initiates protein-kinase-D1-mediated ROS signaling.
C. F. Cowell, H. Doppler, I. K. Yan, A. Hausser, Y. Umezawa, and P. Storz (2009)
J. Cell Sci. 122, 919-928
   Abstract »    Full Text »    PDF »
Amino acid regulation of TOR complex 1.
J. Avruch, X. Long, S. Ortiz-Vega, J. Rapley, A. Papageorgiou, and N. Dai (2009)
Am J Physiol Endocrinol Metab 296, E592-E602
   Abstract »    Full Text »    PDF »
Regulation of mTORC1 and mTORC2 Complex Assembly by Phosphatidic Acid: Competition with Rapamycin.
A. Toschi, E. Lee, L. Xu, A. Garcia, N. Gadir, and D. A. Foster (2009)
Mol. Cell. Biol. 29, 1411-1420
   Abstract »    Full Text »    PDF »
Role of acylglycerol kinase in LPA-induced IL-8 secretion and transactivation of epidermal growth factor-receptor in human bronchial epithelial cells.
S. Kalari, Y. Zhao, E. Wm. Spannhake, E. V. Berdyshev, and V. Natarajan (2009)
Am J Physiol Lung Cell Mol Physiol 296, L328-L336
   Abstract »    Full Text »    PDF »
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M. Y. Zhao, A. Auerbach, A. M. D'Costa, A. P. Rapoport, A. M. Burger, E. A. Sausville, S. A. Stass, F. Jiang, A. M. Sands, N. Aguilera, et al. (2009)
Clin. Cancer Res. 15, 1708-1720
   Abstract »    Full Text »    PDF »
Curcumin Disrupts the Mammalian Target of Rapamycin-Raptor Complex.
C. S. Beevers, L. Chen, L. Liu, Y. Luo, N. J.G. Webster, and S. Huang (2009)
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   Abstract »    Full Text »    PDF »
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R. Tapia, M. Huerta, S. Islas, A. Avila-Flores, E. Lopez-Bayghen, J. Weiske, O. Huber, and L. Gonzalez-Mariscal (2009)
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   Abstract »    Full Text »    PDF »
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C. A. Kraft, J. L. Garrido, E. Fluharty, L. Leiva-Vega, and G. Romero (2008)
J. Biol. Chem. 283, 36636-36645
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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S. M. Knoepp, M. S. Chahal, Y. Xie, Z. Zhang, D. J. Brauner, M. A. Hallman, S. A. Robinson, S. Han, M. Imai, S. Tomlinson, et al. (2008)
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   Abstract »    Full Text »    PDF »
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R. Guo, C.-K. Wan, J. H. Carpenter, T. Mousallem, R.-M. N. Boustany, C.-T. Kuan, A. W. Burks, and X.-P. Zhong (2008)
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   Abstract »    Full Text »    PDF »
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C. A. Farah, I. Nagakura, D. Weatherill, X. Fan, and W. S. Sossin (2008)
Mol. Cell. Biol. 28, 4719-4733
   Abstract »    Full Text »    PDF »
Apolipoprotein L1, a Novel Bcl-2 Homology Domain 3-only Lipid-binding Protein, Induces Autophagic Cell Death.
G. Wan, S. Zhaorigetu, Z. Liu, R. Kaini, Z. Jiang, and C.-a. A. Hu (2008)
J. Biol. Chem. 283, 21540-21549
   Abstract »    Full Text »    PDF »
Dietary Energy Restriction Modulates the Activity of AMP-Activated Protein Kinase, Akt, and Mammalian Target of Rapamycin in Mammary Carcinomas, Mammary Gland, and Liver.
W. Jiang, Z. Zhu, and H. J. Thompson (2008)
Cancer Res. 68, 5492-5499
   Abstract »    Full Text »    PDF »
Honokiol Suppresses Survival Signals Mediated by Ras-Dependent Phospholipase D Activity in Human Cancer Cells.
A. Garcia, Y. Zheng, C. Zhao, A. Toschi, J. Fan, N. Shraibman, H. A. Brown, D. Bar-Sagi, D. A. Foster, and J. L. Arbiser (2008)
Clin. Cancer Res. 14, 4267-4274
   Abstract »    Full Text »    PDF »
Reduced heart size and increased myocardial fuel substrate oxidation in ACC2 mutant mice.
M. F. Essop, H. S. Camp, C. S. Choi, S. Sharma, R. M. Fryer, G. A. Reinhart, P. H. Guthrie, A. Bentebibel, Z. Gu, G. I. Shulman, et al. (2008)
Am J Physiol Heart Circ Physiol 295, H256-H265
   Abstract »    Full Text »    PDF »
Phospholipase D1 is an effector of Rheb in the mTOR pathway.
Y. Sun, Y. Fang, M.-S. Yoon, C. Zhang, M. Roccio, F. J. Zwartkruis, M. Armstrong, H. A. Brown, and J. Chen (2008)
PNAS 105, 8286-8291
   Abstract »    Full Text »    PDF »
Cardiac Restricted Overexpression of Kinase-dead Mammalian Target of Rapamycin (mTOR) Mutant Impairs the mTOR-mediated Signaling and Cardiac Function.
W.-H. Shen, Z. Chen, S. Shi, H. Chen, W. Zhu, A. Penner, G. Bu, W. Li, D. W. Boyle, M. Rubart, et al. (2008)
J. Biol. Chem. 283, 13842-13849
   Abstract »    Full Text »    PDF »
CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1.
T. T. Murooka, R. Rahbar, L. C. Platanias, and E. N. Fish (2008)
Blood 111, 4892-4901
   Abstract »    Full Text »    PDF »
Sulphur and nitrogen regulation of the protease-encoding ACP1 gene in the fungus Botrytis cinerea: correlation with a phospholipase D activity.
S. G. Rolland and C. A. Bruel (2008)
Microbiology 154, 1464-1473
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