Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

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}

Mutant Ras Elevates Dependence on Serum Lipids and Creates a Synthetic Lethality for Rapamycin.
D. Salloum, S. Mukhopadhyay, K. Tung, A. Polonetskaya, and D. A. Foster (2014)
Mol. Cancer Ther. 13, 733-741
   Abstract »    Full Text »    PDF »
Hepatic Gluconeogenesis Is Enhanced by Phosphatidic Acid Which Remains Uninhibited by Insulin in Lipodystrophic Agpat2-/- Mice.
S. Sankella, A. Garg, J. D. Horton, and A. K. Agarwal (2014)
J. Biol. Chem. 289, 4762-4777
   Abstract »    Full Text »    PDF »
The Role of Diacylglycerol Kinase {zeta} and Phosphatidic Acid in the Mechanical Activation of Mammalian Target of Rapamycin (mTOR) Signaling and Skeletal Muscle Hypertrophy.
J.-S. You, H. C. Lincoln, C.-R. Kim, J. W. Frey, C. A. Goodman, X.-P. Zhong, and T. A. Hornberger (2014)
J. Biol. Chem. 289, 1551-1563
   Abstract »    Full Text »    PDF »
Phospholipase D2 Mediates Survival Signaling through Direct Regulation of Akt in Glioblastoma Cells.
R. C. Bruntz, H. E. Taylor, C. W. Lindsley, and H. A. Brown (2014)
J. Biol. Chem. 289, 600-616
   Abstract »    Full Text »    PDF »
Temporal Production of the Signaling Lipid Phosphatidic Acid by Phospholipase D2 Determines the Output of Extracellular Signal-Regulated Kinase Signaling in Cancer Cells.
F. Zhang, Z. Wang, M. Lu, Y. Yonekubo, X. Liang, Y. Zhang, P. Wu, Y. Zhou, S. Grinstein, J. F. Hancock, et al. (2014)
Mol. Cell. Biol. 34, 84-95
   Abstract »    Full Text »    PDF »
Phosphatidic Acid Interacts with a MYB Transcription Factor and Regulates Its Nuclear Localization and Function in Arabidopsis.
H. Yao, G. Wang, L. Guo, and X. Wang (2013)
PLANT CELL 25, 5030-5042
   Abstract »    Full Text »    PDF »
Distinct amino acid-sensing mTOR pathways regulate skeletal myogenesis.
M.-S. Yoon and J. Chen (2013)
Mol. Biol. Cell 24, 3754-3763
   Abstract »    Full Text »    PDF »
Impaired Phosphorylation and Ubiquitination by p70 S6 Kinase (p70S6K) and Smad Ubiquitination Regulatory Factor 1 (Smurf1) Promote Tribbles Homolog 2 (TRIB2) Stability and Carcinogenic Property in Liver Cancer.
J. Wang, Y. Zhang, W. Weng, Y. Qiao, L. Ma, W. Xiao, Y. Yu, Q. Pan, and F. Sun (2013)
J. Biol. Chem. 288, 33667-33681
   Abstract »    Full Text »    PDF »
Diacylglycerol Kinase {zeta} Limits B Cell Antigen Receptor-Dependent Activation of ERK Signaling to Inhibit Early Antibody Responses.
M. L. Wheeler, M. B. Dong, R. Brink, X.-P. Zhong, and A. L. DeFranco (2013)
Science Signaling 6, ra91
   Abstract »    Full Text »    PDF »
The phosphatidylinositol-transfer protein Nir2 binds phosphatidic acid and positively regulates phosphoinositide signalling.
S. Kim, A. Kedan, M. Marom, N. Gavert, O. Keinan, M. Selitrennik, O. Laufman, and S. Lev (2013)
EMBO Rep. 14, 891-899
   Abstract »    Full Text »    PDF »
A recollection of mTOR signaling in learning and memory.
T. E. Graber, P. K. McCamphill, and W. S. Sossin (2013)
Learn. Mem. 20, 518-530
   Abstract »    Full Text »    PDF »
Phosphatidic Acid (PA) Binds PP2AA1 to Regulate PP2A Activity and PIN1 Polar Localization.
H.-B. Gao, Y.-J. Chu, and H.-W. Xue (2013)
Mol Plant 6, 1692-1702
   Abstract »    Full Text »    PDF »
TGF-{beta}/Smad3 activates mammalian target of rapamycin complex-1 to promote collagen production by increasing HIF-1{alpha} expression.
B. Rozen-Zvi, T. Hayashida, S. C. Hubchak, C. Hanna, L. C. Platanias, and H. William Schnaper (2013)
Am J Physiol Renal Physiol 305, F485-F494
   Abstract »    Full Text »    PDF »
cAMP-stimulated transcription of DGK{theta} requires steroidogenic factor 1 and sterol regulatory element binding protein 1.
K. Cai and M. B. Sewer (2013)
J. Lipid Res. 54, 2121-2132
   Abstract »    Full Text »    PDF »
NMR- and Circular Dichroism-monitored Lipid Binding Studies Suggest a General Role for the FATC Domain as Membrane Anchor of Phosphatidylinositol 3-Kinase-related Kinases (PIKK).
L. A. M. Sommer, M. Schaad, and S. A. Dames (2013)
J. Biol. Chem. 288, 20046-20063
   Abstract »    Full Text »    PDF »
Phosphatidic acid is required for the constitutive ruffling and macropinocytosis of phagocytes.
M. Bohdanowicz, D. Schlam, M. Hermansson, D. Rizzuti, G. D. Fairn, T. Ueyama, P. Somerharju, G. Du, and S. Grinstein (2013)
Mol. Biol. Cell 24, 1700-1712
   Abstract »    Full Text »    PDF »
Histone Deacetylase 3 Suppression Increases PH Domain and Leucine-rich Repeat Phosphatase (Phlpp)1 Expression in Chondrocytes to Suppress Akt Signaling and Matrix Secretion.
E. W. Bradley, L. R. Carpio, and J. J. Westendorf (2013)
J. Biol. Chem. 288, 9572-9582
   Abstract »    Full Text »    PDF »
The Phosphatidic Acid Binding Site of the Arabidopsis Trigalactosyldiacylglycerol 4 (TGD4) Protein Required for Lipid Import into Chloroplasts.
Z. Wang, N. S. Anderson, and C. Benning (2013)
J. Biol. Chem. 288, 4763-4771
   Abstract »    Full Text »    PDF »
Mice with an adipocyte-specific lipin 1 separation-of-function allele reveal unexpected roles for phosphatidic acid in metabolic regulation.
M. S. Mitra, Z. Chen, H. Ren, T. E. Harris, K. T. Chambers, A. M. Hall, K. Nadra, S. Klein, R. Chrast, X. Su, et al. (2013)
PNAS 110, 642-647
   Abstract »    Full Text »    PDF »
Role of Phospholipids in Endocytosis, Phagocytosis, and Macropinocytosis.
M. Bohdanowicz and S. Grinstein (2013)
Physiol Rev 93, 69-106
   Abstract »    Full Text »    PDF »
Mammalian Target of Rapamycin (mTOR) Signaling Network in Skeletal Myogenesis.
Y. Ge and J. Chen (2012)
J. Biol. Chem. 287, 43928-43935
   Abstract »    Full Text »    PDF »
Phosphatidic acid regulation of PIPKI is critical for actin cytoskeletal reorganization.
A. N. Roach, Z. Wang, P. Wu, F. Zhang, R. B. Chan, Y. Yonekubo, G. Di Paolo, A. A. Gorfe, and G. Du (2012)
J. Lipid Res. 53, 2598-2609
   Abstract »    Full Text »    PDF »
5-aminosalicylic acid inhibits cell cycle progression in a phospholipase D dependent manner in colorectal cancer.
B. Baan, A. A. Dihal, E. Hoff, C. L. Bos, P. W. Voorneveld, P. J. Koelink, M. E. Wildenberg, V. Muncan, J. Heijmans, H. W. Verspaget, et al. (2012)
Gut 61, 1708-1715
   Abstract »    Full Text »    PDF »
Recent progress on type II diacylglycerol kinases: the physiological functions of diacylglycerol kinase {delta}, {eta} and {kappa} and their involvement in disease.
H. Sakai and F. Sakane (2012)
J. Biochem. 152, 397-406
   Abstract »    Full Text »    PDF »
Diabetes Diminishes Phosphatidic Acid in the Retina: A Putative Mediator for Reduced mTOR Signaling and Increased Neuronal Cell Death.
T. E. Fox, M. M. Young, M. M. Pedersen, X. Han, T. W. Gardner, and M. Kester (2012)
Invest. Ophthalmol. Vis. Sci. 53, 7257-7267
   Abstract »    Full Text »    PDF »
Phosphatidic acid mediates the targeting of tBid to induce lysosomal membrane permeabilization and apoptosis.
K. Zhao, H. Zhou, X. Zhao, D. W. Wolff, Y. Tu, H. Liu, T. Wei, and F. Yang (2012)
J. Lipid Res. 53, 2102-2114
   Abstract »    Full Text »    PDF »
Interactions between the PDZ domains of Bazooka (Par-3) and phosphatidic acid: in vitro characterization and role in epithelial development.
C. G. Yu and T. J. C. Harris (2012)
Mol. Biol. Cell 23, 3743-3753
   Abstract »    Full Text »    PDF »
PERK Utilizes Intrinsic Lipid Kinase Activity To Generate Phosphatidic Acid, Mediate Akt Activation, and Promote Adipocyte Differentiation.
E. Bobrovnikova-Marjon, D. Pytel, M. J. Riese, L. P. Vaites, N. Singh, G. A. Koretzky, E. S. Witze, and J. A. Diehl (2012)
Mol. Cell. Biol. 32, 2268-2278
   Abstract »    Full Text »    PDF »
Lipid metabolism in skeletal muscle: generation of adaptive and maladaptive intracellular signals for cellular function.
M. J. Watt and A. J. Hoy (2012)
Am J Physiol Endocrinol Metab 302, E1315-E1328
   Abstract »    Full Text »    PDF »
Phospholipase D2: A Pivotal Player Modulating RBL-2H3 Mast Cell Structure.
C. M. M. Marchini-Alves, L. M. Nicoletti, V. M. Mazucato, L. B. de Souza, T. Hitomi, C. d. P. Alves, M. C. Jamur, and C. Oliver (2012)
Journal of Histochemistry & Cytochemistry 60, 386-396
   Abstract »    Full Text »    PDF »
Phospholipase D and mTORC1: Nutrients Are What Bring Them Together.
B. M. Wiczer and G. Thomas (2012)
Science Signaling 5, pe13
   Abstract »    Full Text »    PDF »
c-Abl Tyrosine Kinase Regulates Serum-induced Nuclear Export of Diacylglycerol Kinase {alpha} by Phosphorylation at Tyr-218.
T. Matsubara, M. Ikeda, Y. Kiso, M. Sakuma, K.-i. Yoshino, F. Sakane, I. Merida, N. Saito, and Y. Shirai (2012)
J. Biol. Chem. 287, 5507-5517
   Abstract »    Full Text »    PDF »
Regulation of TOR by small GTPases.
R. V. Duran and M. N. Hall (2012)
EMBO Rep. 13, 121-128
   Abstract »    Full Text »    PDF »
CGI-58/ABHD5-Derived Signaling Lipids Regulate Systemic Inflammation and Insulin Action.
C. C. Lord, J. L. Betters, P. T. Ivanova, S. B. Milne, D. S. Myers, J. Madenspacher, G. Thomas, S. Chung, M. Liu, M. A. Davis, et al. (2012)
Diabetes 61, 355-363
   Abstract »    Full Text »    PDF »
Glycerolipid signals alter mTOR complex 2 (mTORC2) to diminish insulin signaling.
C. Zhang, A. A. Wendel, M. R. Keogh, T. E. Harris, J. Chen, and R. A. Coleman (2012)
PNAS 109, 1667-1672
   Abstract »    Full Text »    PDF »
Phospholipase D2 (PLD2) Shortens the Time Required for Myeloid Leukemic Cell Differentiation: MECHANISM OF ACTION.
M. Di Fulvio, K. Frondorf, K. M. Henkels, W. C. Grunwald Jr., D. Cool, and J. Gomez-Cambronero (2012)
J. Biol. Chem. 287, 393-407
   Abstract »    Full Text »    PDF »
Relationship of glucose and oleate metabolism to cardiac function in lipin-1 deficient (fld) mice.
B. P. C. Kok, P. C. Kienesberger, J. R. B. Dyck, and D. N. Brindley (2012)
J. Lipid Res. 53, 105-118
   Abstract »    Full Text »    PDF »
Functional Characterization of the Interaction between Bacterial Adhesin Multivalent Adhesion Molecule 7 (MAM7) Protein and Its Host Cell Ligands.
A. M. Krachler and K. Orth (2011)
J. Biol. Chem. 286, 38939-38947
   Abstract »    Full Text »    PDF »
Class III PI-3-kinase activates phospholipase D in an amino acid-sensing mTORC1 pathway.
M.-S. Yoon, G. Du, J. M. Backer, M. A. Frohman, and J. Chen (2011)
J. Cell Biol. 195, 435-447
   Abstract »    Full Text »    PDF »
Cigarette Smoke Components Induce Matrix Metalloproteinase-1 in Aortic Endothelial Cells through Inhibition of mTOR Signaling.
V. Lemaitre, A. J. Dabo, and J. D'Armiento (2011)
Toxicol. Sci. 123, 542-549
   Abstract »    Full Text »    PDF »
Spatial regulation of the mTORC1 system in amino acids sensing pathway.
T. Suzuki and K. Inoki (2011)
Acta Biochim Biophys Sin 43, 671-679
   Abstract »    Full Text »    PDF »
Tight Regulation of Diacylglycerol-Mediated Signaling Is Critical for Proper Invariant NKT Cell Development.
S. Shen, J. Wu, S. Srivatsan, B. K. Gorentla, J. Shin, L. Xu, and X.-P. Zhong (2011)
J. Immunol. 187, 2122-2129
   Abstract »    Full Text »    PDF »
Phosphatidic Acid Activates Mammalian Target of Rapamycin Complex 1 (mTORC1) Kinase by Displacing FK506 Binding Protein 38 (FKBP38) and Exerting an Allosteric Effect.
M.-S. Yoon, Y. Sun, E. Arauz, Y. Jiang, and J. Chen (2011)
J. Biol. Chem. 286, 29568-29574
   Abstract »    Full Text »    PDF »
mTORC1 signaling: what we still don't know.
X. Wang and C. G. Proud (2011)
J Mol Cell Biol 3, 206-220
   Abstract »    Full Text »    PDF »
Phospholipase D Mediates Nutrient Input to Mammalian Target of Rapamycin Complex 1 (mTORC1).
L. Xu, D. Salloum, P. S. Medlin, M. Saqcena, P. Yellen, B. Perrella, and D. A. Foster (2011)
J. Biol. Chem. 286, 25477-25486
   Abstract »    Full Text »    PDF »
An Akt-dependent Increase in Canonical Wnt Signaling and a Decrease in Sclerostin Protein Levels Are Involved in Strontium Ranelate-induced Osteogenic Effects in Human Osteoblasts.
M. S. Rybchyn, M. Slater, A. D. Conigrave, and R. S. Mason (2011)
J. Biol. Chem. 286, 23771-23779
   Abstract »    Full Text »    PDF »
The phosphatidylcholine-hydrolysing phospholipase C NPC4 plays a role in response of Arabidopsis roots to salt stress.
D. Kocourkova, Z. Krckova, P. Pejchar, S. Veselkova, O. Valentova, R. Wimalasekera, G. F. E. Scherer, and J. Martinec (2011)
J. Exp. Bot. 62, 3753-3763
   Abstract »    Full Text »    PDF »
Phospholipase D Regulates Myogenic Differentiation through the Activation of Both mTORC1 and mTORC2 Complexes.
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 »
Caloric restriction in leptin deficiency does not correct myocardial steatosis: failure to normalize PPAR{alpha}/PGC1{alpha} and thermogenic glycerolipid/fatty acid cycling.
J. E. Rame, L. A. Barouch, M. N. Sack, E. G. Lynn, M. Abu-Asab, M. Tsokos, S. J. Kern, J. J. Barb, P. J. Munson, M. K. Halushka, et al. (2011)
Physiol Genomics 43, 726-738
   Abstract »    Full Text »    PDF »
Negative regulation of mTOR activation by diacylglycerol kinases.
B. K. Gorentla, C.-K. Wan, and X.-P. Zhong (2011)
Blood 117, 4022-4031
   Abstract »    Full Text »    PDF »
Molecular, cellular, and physiological responses to phosphatidic acid formation in plants.
C. Testerink and T. Munnik (2011)
J. Exp. Bot. 62, 2349-2361
   Abstract »    Full Text »    PDF »
Dual Regulation of RA-RhoGAP Activity by Phosphatidic Acid and Rap1 during Neurite Outgrowth.
T. Kurooka, Y. Yamamoto, Y. Takai, and T. Sakisaka (2011)
J. Biol. Chem. 286, 6832-6843
   Abstract »    Full Text »    PDF »
Cardiac diacylglycerol accumulation in high fat-fed mice is associated with impaired insulin-stimulated glucose oxidation.
L. Zhang, J. R. Ussher, T. Oka, V. J. J. Cadete, C. Wagg, and G. D. Lopaschuk (2011)
Cardiovasc Res 89, 148-156
   Abstract »    Full Text »    PDF »
Cyclic AMP Controls mTOR through Regulation of the Dynamic Interaction between Rheb and Phosphodiesterase 4D.
H. W. Kim, S. H. Ha, M. N. Lee, E. Huston, D.-H. Kim, S. K. Jang, P.-G. Suh, M. D. Houslay, and S. H. Ryu (2010)
Mol. Cell. Biol. 30, 5406-5420
   Abstract »    Full Text »    PDF »
The Molecular Basis of Phospholipase D2-Induced Chemotaxis: Elucidation of Differential Pathways in Macrophages and Fibroblasts.
K. Knapek, K. Frondorf, J. Post, S. Short, D. Cox, and J. Gomez-Cambronero (2010)
Mol. Cell. Biol. 30, 4492-4506
   Abstract »    Full Text »    PDF »
Mammalian Target of Rapamycin (mTOR) Activation Increases Axonal Growth Capacity of Injured Peripheral Nerves.
N. Abe, S. H. Borson, M. J. Gambello, F. Wang, and V. Cavalli (2010)
J. Biol. Chem. 285, 28034-28043
   Abstract »    Full Text »    PDF »
Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway.
J. N. Winter, T. E. Fox, M. Kester, L. S. Jefferson, and S. R. Kimball (2010)
Am J Physiol Cell Physiol 299, C335-C344
   Abstract »    Full Text »    PDF »
Procoagulant and prothrombotic activation of human erythrocytes by phosphatidic acid.
J.-Y. Noh, K.-M. Lim, O.-N. Bae, S.-M. Chung, S.-W. Lee, K.-M. Joo, S.-D. Lee, and J.-H. Chung (2010)
Am J Physiol Heart Circ Physiol 299, H347-H355
   Abstract »    Full Text »    PDF »
Expansion of the target of rapamycin (TOR) kinase family and function in Leishmania shows that TOR3 is required for acidocalcisome biogenesis and animal infectivity.
L. Madeira da Silva and S. M. Beverley (2010)
PNAS 107, 11965-11970
   Abstract »    Full Text »    PDF »
Mammalian Target of Rapamycin (mTOR) and S6 Kinase Down-regulate Phospholipase D2 Basal Expression and Function.
F. Tabatabaian, K. Dougherty, M. Di Fulvio, and J. Gomez-Cambronero (2010)
J. Biol. Chem. 285, 18991-19001
   Abstract »    Full Text »    PDF »
Phosphatidic Acid Is a Leukocyte Chemoattractant That Acts through S6 Kinase Signaling.
K. Frondorf, K. M. Henkels, M. A. Frohman, and J. Gomez-Cambronero (2010)
J. Biol. Chem. 285, 15837-15847
   Abstract »    Full Text »    PDF »
Dependence of Phospholipase D1 Multi-monoubiquitination on Its Enzymatic Activity and Palmitoylation.
H. Yin, Y. Gui, G. Du, M. A. Frohman, and X. L. Zheng (2010)
J. Biol. Chem. 285, 13580-13588
   Abstract »    Full Text »    PDF »
Structural Basis for the Association of the Redox-sensitive Target of Rapamycin FATC Domain with Membrane-mimetic Micelles.
S. A. Dames (2010)
J. Biol. Chem. 285, 7766-7775
   Abstract »    Full Text »    PDF »
Genetic Susceptibility Factors in a Cohort of 38 Patients with SAPHO Syndrome: A Study of PSTPIP2, NOD2, and LPIN2 Genes.
J Rheumatol 37, 401-409
   Abstract »    Full Text »    PDF »
Diacylglycerol Kinase {epsilon} Is Selective for Both Acyl Chains of Phosphatidic Acid or Diacylglycerol.
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)
J. Biol. Chem. 284, 31062-31073
   Abstract »    Full Text »    PDF »
At4g24160, a Soluble Acyl-Coenzyme A-Dependent Lysophosphatidic Acid Acyltransferase.
A. K. Ghosh, N. Chauhan, S. Rajakumari, G. Daum, and R. Rajasekharan (2009)
Plant Physiology 151, 869-881
   Abstract »    Full Text »    PDF »
The Tyrosine Kinase Fer Is a Downstream Target of the PLD-PA Pathway that Regulates Cell Migration.
T. Itoh, J. Hasegawa, K. Tsujita, Y. Kanaho, and T. Takenawa (2009)
Science Signaling 2, ra52
   Abstract »    Full Text »    PDF »
Enzymatic measurement of phosphatidic acid in cultured cells.
S.-y. Morita, K. Ueda, and S. Kitagawa (2009)
J. Lipid Res. 50, 1945-1952
   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 »
Phospho-p70S6K/p85S6K and cdc2/cdk1 Are Novel Targets for Diffuse Large B-Cell Lymphoma Combination Therapy.
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)
Cancer Res. 69, 1000-1008
   Abstract »    Full Text »    PDF »
Zona Occludens-2 Inhibits Cyclin D1 Expression and Cell Proliferation and Exhibits Changes in Localization along the Cell Cycle.
R. Tapia, M. Huerta, S. Islas, A. Avila-Flores, E. Lopez-Bayghen, J. Weiske, O. Huber, and L. Gonzalez-Mariscal (2009)
Mol. Biol. Cell 20, 1102-1117
   Abstract »    Full Text »    PDF »
Role of Phosphatidic Acid in the Coupling of the ERK Cascade.
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 »
Differential Dependence of Hypoxia-inducible Factors 1{alpha} and 2{alpha} on mTORC1 and mTORC2.
A. Toschi, E. Lee, N. Gadir, M. Ohh, and D. A. Foster (2008)
J. Biol. Chem. 283, 34495-34499
   Abstract »    Full Text »    PDF »
Effects of Active and Inactive Phospholipase D2 on Signal Transduction, Adhesion, Migration, Invasion, and Metastasis in EL4 Lymphoma Cells.
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)
Mol. Pharmacol. 74, 574-584
   Abstract »    Full Text »    PDF »
Synergistic control of T cell development and tumor suppression by diacylglycerol kinase {alpha} and {zeta}.
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)
PNAS 105, 11909-11914
   Abstract »    Full Text »    PDF »
Physiological Role for Phosphatidic Acid in the Translocation of the Novel Protein Kinase C Apl II in Aplysia Neurons.
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
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882