Genomes and Genes
Summary: Fatty acid derivatives of glycerophosphates. They are composed of glycerol bound in ester linkage with 1 mole of phosphoric acid at the terminal 3-hydroxyl group and with 2 moles of fatty acids at the other two hydroxyl groups.
- Lehman N, Ledford B, Di Fulvio M, Frondorf K, McPhail L, Gomez Cambronero J. Phospholipase D2-derived phosphatidic acid binds to and activates ribosomal p70 S6 kinase independently of mTOR. FASEB J. 2007;21:1075-87 pubmed..These results show for the first time a direct (mTOR-independent) participation of PLD in the p70S6K pathway and implicate PA as a nexus that brings together cell phospholipases and kinases. ..
- Asp L, Kartberg F, Fernandez Rodriguez J, Smedh M, Elsner M, Laporte F, et al. Early stages of Golgi vesicle and tubule formation require diacylglycerol. Mol Biol Cell. 2009;20:780-90 pubmed publisher..Rather, knockdown of ARFGAP1 results in an increase in membrane buds and a decrease of vesicles and tubules suggesting it functions in the late stages of scission. How DAG promotes bud formation is discussed. ..
- Yu Z, Zhang J, Wang X, Chen J. Excessive copper induces the production of reactive oxygen species, which is mediated by phospholipase D, nicotinamide adenine dinucleotide phosphate oxidase and antioxidant systems. J Integr Plant Biol. 2008;50:157-67 pubmed publisher..This evidence suggests that excessive Cu2+-elevated reactive oxygen species (ROS) production is caused by upregulated PLD that elevates the activity of NADPH oxidase and its collapsed antioxidant systems that scavenges ROS. ..
- Zhang Y, Du G. Phosphatidic acid signaling regulation of Ras superfamily of small guanosine triphosphatases. Biochim Biophys Acta. 2009;1791:850-5 pubmed publisher..Some future directions and the implication of PA regulation of Ras small GTPases in pathology are also discussed. ..
- Klimecka M, Szczegielniak J, Godecka L, Lewandowska Gnatowska E, Dobrowolska G, Muszy ska G. Regulation of wound-responsive calcium-dependent protein kinase from maize (ZmCPK11) by phosphatidic acid. Acta Biochim Pol. 2011;58:589-95 pubmed..The influence of PA on the activity and transcript level of ZmCPK11 suggests an involvement of this kinase in a PA-mediated wound signal transduction pathway...
- Frondorf K, Henkels K, Frohman M, Gomez Cambronero J. Phosphatidic acid is a leukocyte chemoattractant that acts through S6 kinase signaling. J Biol Chem. 2010;285:15837-47 pubmed publisher..In summary, we report the discovery of PA as a leukocyte chemoattractant via cell entry and activation of S6K to mediate the cytoskeletal actin polymerization and leukocyte chemotaxis required for the immune function of these cells. ..
- Dubots E, Audry M, Yamaryo Y, Bastien O, Ohta H, Breton C, et al. Activation of the chloroplast monogalactosyldiacylglycerol synthase MGD1 by phosphatidic acid and phosphatidylglycerol. J Biol Chem. 2010;285:6003-11 pubmed publisher..Activation of MGD1 by PA and PG is proposed as an important mechanism coupling phospholipid and galactolipid syntheses in plants. ..
- Morita S, Ueda K, Kitagawa S. Enzymatic measurement of phosphatidic acid in cultured cells. J Lipid Res. 2009;50:1945-52 pubmed publisher..This novel method for PA quantification is simple, rapid, specific, sensitive, and high-throughput and will help to study the biological functions of PA and its related enzymes. ..
- Zhang J, Zheng X, Yang X, Liao K. CIN85 associates with endosomal membrane and binds phosphatidic acid. Cell Res. 2009;19:733-46 pubmed publisher..Taken together, our results suggest that CIN85 may function as a scaffold molecule in both the internalization and endocytic cargo sorting processes through its association with the endosomal membrane. ..
- Carman G, Henry S. Phosphatidic acid plays a central role in the transcriptional regulation of glycerophospholipid synthesis in Saccharomyces cerevisiae. J Biol Chem. 2007;282:37293-7 pubmed
- Raghu P, Manifava M, Coadwell J, Ktistakis N. Emerging findings from studies of phospholipase D in model organisms (and a short update on phosphatidic acid effectors). Biochim Biophys Acta. 2009;1791:889-97 pubmed publisher..At the end of this review we will also provide a short update on phosphatidic acid targets, a topic last reviewed in 2006. ..
- Kooijman E, Burger K. Biophysics and function of phosphatidic acid: a molecular perspective. Biochim Biophys Acta. 2009;1791:881-8 pubmed publisher..Diverse examples from recent literature in support of this model will be presented and the broader implications of our findings will be discussed. ..
- Zhang Y, Zhu H, Zhang Q, Li M, Yan M, Wang R, et al. Phospholipase dalpha1 and phosphatidic acid regulate NADPH oxidase activity and production of reactive oxygen species in ABA-mediated stomatal closure in Arabidopsis. Plant Cell. 2009;21:2357-77 pubmed publisher..Thus, PA is as a central lipid signaling molecule that links different components in the ABA signaling network in guard cells. ..
- Yu L, Nie J, Cao C, Jin Y, Yan M, Wang F, et al. Phosphatidic acid mediates salt stress response by regulation of MPK6 in Arabidopsis thaliana. New Phytol. 2010;188:762-73 pubmed publisher..The MPK6 phosphorylation of SOS1 was stimulated by treatment with NaCl, as well as directly by PA. • These results suggest that PA plays a critical role in coupling MAPK cascades in response to salt stress. ..
- Xu L, Salloum D, Medlin P, Saqcena M, Yellen P, Perrella B, et al. Phospholipase D mediates nutrient input to mammalian target of rapamycin complex 1 (mTORC1). J Biol Chem. 2011;286:25477-86 pubmed publisher..Thus, a key stimulatory event for mTORC1 activation in response to nutrients is the generation of phosphatidic acid by PLD. ..
- Bargmann B, Laxalt A, ter Riet B, Testerink C, Merquiol E, Mosblech A, et al. Reassessing the role of phospholipase D in the Arabidopsis wounding response. Plant Cell Environ. 2009;32:837-50 pubmed publisher..Moreover, larvae of the Cabbage White butterfly (Pieris rapae) grew equally well on wild-type and the pld knock-out mutants. ..
- Tsukahara T, Tsukahara R, Fujiwara Y, Yue J, Cheng Y, Guo H, et al. Phospholipase D2-dependent inhibition of the nuclear hormone receptor PPARgamma by cyclic phosphatidic acid. Mol Cell. 2010;39:421-32 pubmed publisher..We conclude that CPA is a second messenger and a physiological inhibitor of PPARgamma, revealing that PPARgamma is regulated by endogenous agonists as well as by antagonists. ..
- Testerink C, Munnik T. Molecular, cellular, and physiological responses to phosphatidic acid formation in plants. J Exp Bot. 2011;62:2349-61 pubmed publisher..Through characterization of several of these PA targets, a molecular and genetic basis for PA's role in plant stress and development is emerging. ..
- Nishikimi A, Fukuhara H, Su W, Hongu T, Takasuga S, Mihara H, et al. Sequential regulation of DOCK2 dynamics by two phospholipids during neutrophil chemotaxis. Science. 2009;324:384-7 pubmed publisher..Thus, intracellular DOCK2 dynamics are sequentially regulated by distinct phospholipids to localize Rac activation during neutrophil chemotaxis. ..
- Bereczki E, Re F, Masserini M, Winblad B, Pei J. Liposomes functionalized with acidic lipids rescue A?-induced toxicity in murine neuroblastoma cells. Nanomedicine. 2011;7:560-71 pubmed publisher..We also detected rescue of the imbalance of GSK-3? and PP2A activity, and reduction in tau phosphorylation. Thus, these liposomes appear particularly suitable for implementing further therapeutic strategies for AD. ..
- Zhao C, Du G, Skowronek K, Frohman M, Bar Sagi D. Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos. Nat Cell Biol. 2007;9:706-12 pubmed..Our findings establish a crucial role for PLD2 in the coupling of extracellular signals to Sos-mediated Ras activation, and provide new insights into the spatial coordination of this activation event. ..
- Foster D. Regulation of mTOR by phosphatidic acid?. Cancer Res. 2007;67:1-4 pubmed..In this review, 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. ..
- Jang J, Lee C, Hwang D, Ryu S. Understanding of the roles of phospholipase D and phosphatidic acid through their binding partners. Prog Lipid Res. 2012;51:71-81 pubmed publisher..The PLD network suggests that PLD and PA could act as a decision maker and/or as a coordinator of signal dynamics. This viewpoint provides a turning point for understanding the roles of PLD-PA as a dynamic signaling hub. ..
- Raja M, Spelbrink R, de Kruijff B, Killian J. Phosphatidic acid plays a special role in stabilizing and folding of the tetrameric potassium channel KcsA. FEBS Lett. 2007;581:5715-22 pubmed..The data indicate that PA creates some specificity over PG, and that it most likely stabilizes the tetramer via both electrostatic and hydrogen bond interactions...
- Sun Y, Chen J. mTOR signaling: PLD takes center stage. Cell Cycle. 2008;7:3118-23 pubmed..We also consider the implications from several recent findings and propose mechanistic models of PLD-mTOR signaling to be tested in the near future. ..
- Zhong X, Guo R, Zhou H, Liu C, Wan C. Diacylglycerol kinases in immune cell function and self-tolerance. Immunol Rev. 2008;224:249-64 pubmed publisher..These studies demonstrate pivotal roles of DGKs in regulating immune cell function by acting both as signal terminator and initiator. ..
- Liu C, Machado F, Guo R, Nichols K, Burks A, Aliberti J, et al. Diacylglycerol kinase zeta regulates microbial recognition and host resistance to Toxoplasma gondii. J Exp Med. 2007;204:781-92 pubmed
- Roach A, Wang Z, Wu P, Zhang F, Chan R, Yonekubo Y, et al. Phosphatidic acid regulation of PIPKI is critical for actin cytoskeletal reorganization. J Lipid Res. 2012;53:2598-609 pubmed publisher..Taken together, these results reveal a new molecular mechanism through which PA regulates PIPKI and provides direct evidence that PA is important for the localization and functions of PIPKI in intact cells. ..
- Sato T, Hongu T, Sakamoto M, Funakoshi Y, Kanaho Y. Molecular mechanisms of N-formyl-methionyl-leucyl-phenylalanine-induced superoxide generation and degranulation in mouse neutrophils: phospholipase D is dispensable. Mol Cell Biol. 2013;33:136-45 pubmed publisher..These results demonstrate that conventional protein kinase C (cPKC) is crucial for superoxide generation, and a Ca(2+)-dependent signaling pathway(s) and cPKC are involved in degranulation in mouse neutrophils. ..
- O Neil T, Duffy L, Frey J, Hornberger T. The role of phosphoinositide 3-kinase and phosphatidic acid in the regulation of mammalian target of rapamycin following eccentric contractions. J Physiol. 2009;587:3691-701 pubmed publisher..Combined, the results of this study indicate that the activation of mTOR following eccentric contractions occurs through a PI3K-PKB-independent mechanism that requires PLD and PA. ..
- Tsukahara T, Hanazawa S, Murakami Murofushi K. Cyclic phosphatidic acid influences the expression and regulation of cyclic nucleotide phosphodiesterase 3B and lipolysis in 3T3-L1 cells. Biochem Biophys Res Commun. 2011;404:109-14 pubmed publisher..These findings contribute to the participation of cPA on the lipolytic activity in 3T3-L1 adipocytes. Our studies imply that cPA might be a therapeutic compound in the treatment of obesity and obesity-related diseases. ..
- Foster D. Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells. Biochim Biophys Acta. 2009;1791:949-55 pubmed publisher..This review summarizes the role of PA in regulating the mTOR-mediated signals that promote cancer cell survival. ..
- Cho J, Hong S, Kim E, Park S, Park C, Kim J, et al. Overexpression of phospholipase D suppresses taxotere-induced cell death in stomach cancer cells. Biochim Biophys Acta. 2008;1783:912-23 pubmed publisher..Taken together, PLD1 and PLD2 are closely related with Bcl-2 expression together with PLA(2), but not with PAP, during taxotere-induced apoptosis in SNU 484 cells. ..
- Kooijman E, Tieleman D, Testerink C, Munnik T, Rijkers D, Burger K, et al. An electrostatic/hydrogen bond switch as the basis for the specific interaction of phosphatidic acid with proteins. J Biol Chem. 2007;282:11356-64 pubmed..In combination with the special packing properties of PA, PA may well be nature's preferred membrane lipid for interfacial insertion of positively charged membrane protein domains. ..
- Nelson C, Perry S, Regier D, Prescott S, Topham M, Lefkowitz R. Targeting of diacylglycerol degradation to M1 muscarinic receptors by beta-arrestins. Science. 2007;315:663-6 pubmed..Thus, beta-arrestins can serve similar regulatory functions for disparate classes of 7TMRs through structurally dissimilar enzymes that degrade chemically distinct second messengers. ..
- Guo L, Mishra G, Taylor K, Wang X. Phosphatidic acid binds and stimulates Arabidopsis sphingosine kinases. J Biol Chem. 2011;286:13336-45 pubmed publisher..The PA-SPHK interaction depends on the PA molecular species. The data suggest that these two Arabidopsis SPHKs are molecular targets of PA, and the PA stimulation of SPHK is part of the signaling networks in Arabidopsis. ..
- Cai J, Abramovici H, Gee S, Topham M. Diacylglycerol kinases as sources of phosphatidic acid. Biochim Biophys Acta. 2009;1791:942-8 pubmed publisher..In other cases, DGKs broadly regulate signaling events by virtue of their ability to provide PA for the synthesis of phosphatidylinositols (PtdIns). ..
- Hong Y, Devaiah S, Bahn S, Thamasandra B, Li M, Welti R, et al. Phospholipase D epsilon and phosphatidic acid enhance Arabidopsis nitrogen signaling and growth. Plant J. 2009;58:376-87 pubmed publisher..The lipid-signaling process may play a role in connecting membrane sensing of nutrient status to increased plant growth and biomass production. ..
- Distéfano A, Garcia Mata C, Lamattina L, Laxalt A. Nitric oxide-induced phosphatidic acid accumulation: a role for phospholipases C and D in stomatal closure. Plant Cell Environ. 2008;31:187-94 pubmed..NO-induced stomatal closure was blocked either when PLC or PLD activity was inhibited. We have shown that PLC- and PLD-derived PA represents a downstream component of NO signalling cascade during stomatal closure...
- Pleskot R, Pejchar P, Zarsky V, Staiger C, Potocky M. Structural insights into the inhibition of actin-capping protein by interactions with phosphatidic acid and phosphatidylinositol (4,5)-bisphosphate. PLoS Comput Biol. 2012;8:e1002765 pubmed publisher..We prepared a GST-fusion protein for the C-terminal domain of plant ? subunit and verified this hypothesis with lipid-binding assays in vitro. ..
- Gupte R, Siddam A, Lu Y, Li W, Fujiwara Y, Panupinthu N, et al. Synthesis and pharmacological evaluation of the stereoisomers of 3-carba cyclic-phosphatidic acid. Bioorg Med Chem Lett. 2010;20:7525-8 pubmed publisher..These results extend the potential utility of these compounds as potential lead compounds warranting evaluation as cancer therapeutics. ..
- Schwarz K, Natarajan S, Kassas N, Vitale N, Schmitz F. The synaptic ribbon is a site of phosphatidic acid generation in ribbon synapses. J Neurosci. 2011;31:15996-6011 pubmed publisher..We propose that PA generated at synaptic ribbons likely facilitates synaptic vesicle trafficking. ..
- Veverka V, Crabbe T, Bird I, Lennie G, Muskett F, Taylor R, et al. Structural characterization of the interaction of mTOR with phosphatidic acid and a novel class of inhibitor: compelling evidence for a central role of the FRB domain in small molecule-mediated regulation of mTOR. Oncogene. 2008;27:585-95 pubmed
- Faraudo J, Travesset A. Phosphatidic acid domains in membranes: effect of divalent counterions. Biophys J. 2007;92:2806-18 pubmed..We conclude with a discussion of the implications of our results in the context of recent experimental studies in model systems and in real cells. ..