In eukaryotic cells, PA 2The abbreviations used are: PAphosphatidic acidDAGdiacylglycerolTAGtriacylglycerolPCphosphatidylcholinePIphosphatidylinositolPEphosphatidylethanolaminePSphosphatidylserineUASINOupstream activating sequence inositol-responsive elementERendoplasmic reticulum is a central precursor for the synthesis of major glycerophospholipids, DAG and TAG, as well as a major signaling lipid. In mammalian cells, PA is implicated as an activator of cell growth and proliferation, vesicular trafficking, secretion, and endocytosis (1Waggoner D.W. Xu J. Singh I. Jasinska R. Zhang Q.X. Brindley D.N. Biochim. Biophys. Acta. 1999; 1439: 299-316Crossref PubMed Scopus (114) Google Scholar, 2Sciorra V.A. Morris A.J. Biochim. Biophys. Acta. 2002; 1582: 45-51Crossref PubMed Scopus (145) Google Scholar, 3Testerink C. Munnik T. Trends Plant Sci. 2005; 10: 368-375Abstract Full Text Full Text PDF PubMed Scopus (462) Google Scholar, 4Wang X. Devaiah S.P. Zhang W. Welti R. Prog. Lipid Res. 2006; 45: 250-278Crossref PubMed Scopus (577) Google Scholar, 5Brindley D.N. J. Cell. Biochem. 2004; 92: 900-912Crossref PubMed Scopus (185) Google Scholar, 6Howe A.G. McMaster C.R. Can. J. Physiol. Pharmacol. 2006; 84: 29-38Crossref PubMed Google Scholar, 7Foster D.A. Cancer Res. 2007; 67: 1-4Crossref PubMed Scopus (139) Google Scholar). In plants, PA is implicated in seed germination and response to stress induced by drought, salinity, and low temperature (3Testerink C. Munnik T. Trends Plant Sci. 2005; 10: 368-375Abstract Full Text Full Text PDF PubMed Scopus (462) Google Scholar, 4Wang X. Devaiah S.P. Zhang W. Welti R. Prog. Lipid Res. 2006; 45: 250-278Crossref PubMed Scopus (577) Google Scholar). phosphatidic acid diacylglycerol triacylglycerol phosphatidylcholine phosphatidylinositol phosphatidylethanolamine phosphatidylserine upstream activating sequence inositol-responsive element endoplasmic reticulum The signaling roles of PA in the yeast Saccharomyces cerevisiae have not received as much attention as they have in higher eukaryotic cells. However, it is known that PA production via phospholipase D-mediated turnover of PC is necessary for suppression of growth and membrane trafficking defects in mutants defective in Sec14p, an essential PI/PC-binding protein (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 9Sreenivas A. Patton-Vogt J.L. Bruno V. Griac P. Henry S.A. J. Biol. Chem. 1998; 273: 16635-16638Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar, 10Xie Z.G. Fang M. Rivas M.P. Faulkner A.J. Sternweis P.C. Engebrecht J. Bankaitis V.A. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 12346-12351Crossref PubMed Scopus (145) Google Scholar). In addition, PA production via phospholipase D is implicated in Spo20p-mediated fusion of vesicles with the prespore membrane during sporogenesis (11Rudge S.A. Sciorra V.A. Iwamoto M. Zhou C. Strahl T. Morris A.J. Thorner J. Engebrecht J. Mol. Biol. Cell. 2004; 15: 207-218Crossref PubMed Scopus (52) Google Scholar, 12Nakanishi H. Morishita M. Schwartz C.L. Coluccio A. Engebrecht J. Neiman A.M. J. Cell Sci. 2006; 119: 1406-1415Crossref PubMed Scopus (90) Google Scholar). The best studied regulatory function of PA in S. cerevisiae is its role as a signaling molecule in the transcriptional regulation of glycerophospholipid synthesis itself, the major topic of this review. We will focus on the pathways generating and utilizing PA in yeast and the evidence that PA plays a central role in the transcriptional regulation of glycerophospholipid synthesis. PA is the precursor of all membrane glycerophospholipids and the storage lipid TAG in S. cerevisiae (Fig. 1) (13Rattray J.B. Schibeci A. Kidby D.K. Bacteriol. Rev. 1975; 39: 197-231Crossref PubMed Google Scholar, 14Henry S.A. Strathern J.N. Jones E.W. Broach J.R. The Molecular Biology of the Yeast Saccharomyces: Metabolism and Gene Expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1982: 101-158Google Scholar, 15Paltauf F. Kohlwein S.D. Henry S.A. Jones E.W. Pringle J.R. Broach J.R. The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1992: 415-500Google Scholar, 16Czabany T. Athenstaedt K. Daum G. Biochim. Biophys. Acta. 2007; 1771: 299-309Crossref PubMed Scopus (185) Google Scholar). In the de novo pathway, PA is synthesized from glycerol 3-phosphate and then used for the synthesis of glycerophospholipids via the liponucleotide intermediate CDP-DAG (i.e. CDP-DAG pathway) (Fig. 1). PA is also used for the synthesis of PE and PC via DAG in the Kennedy pathway (CDP-ethanolamine and CDP-choline branches, respectively) (Fig. 1). The DAG derived from PA is also used for the synthesis of TAG (Fig. 1). Cells grown in the absence of choline synthesize PC primarily via the CDP-DAG pathway (17McMaster C.R. Bell R.M. J. Biol. Chem. 1994; 269: 14776-14783Abstract Full Text PDF PubMed Google Scholar). In contrast, cells supplemented with choline synthesize PC primarily via the Kennedy pathway (17McMaster C.R. Bell R.M. J. Biol. Chem. 1994; 269: 14776-14783Abstract Full Text PDF PubMed Google Scholar). Nonetheless, PC is synthesized from PA by both the CDP-DAG and Kennedy pathways regardless of whether choline is added to the growth medium (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 18Morash S.C. McMaster C.R. Hjelmstad R.H. Bell R.M. J. Biol. Chem. 1994; 269: 28769-28776Abstract Full Text PDF PubMed Google Scholar, 19McGee T.P. Skinner H.B. Whitters E.A. Henry S.A. Bankaitis V.A. J. Cell Biol. 1994; 124: 273-287Crossref PubMed Scopus (152) Google Scholar, 20McMaster C.R. Bell R.M. J. Biol. Chem. 1994; 269: 28010-28016Abstract Full Text PDF PubMed Google Scholar, 21Ostrander D.B. O'Brien D.J. Gorman J.A. Carman G.M. J. Biol. Chem. 1998; 273: 18992-19001Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar, 22Kim K.-H. Voelker D.R. Flocco M.T. Carman G.M. J. Biol. Chem. 1998; 273: 6844-6852Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar). The choline required is derived from the phospholipase D-mediated turnover of the PC synthesized via the CDP-DAG pathway (Fig. 1) (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 10Xie Z.G. Fang M. Rivas M.P. Faulkner A.J. Sternweis P.C. Engebrecht J. Bankaitis V.A. Proc. Natl. Acad. Sci. U. S. A. 1998; 95: 12346-12351Crossref PubMed Scopus (145) Google Scholar). The PA produced is reincorporated into glycerophospholipids (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar). Mutants defective in PC synthesis via the CDP-DAG pathway require choline for growth; they synthesize PC via the CDP-choline branch of the Kennedy pathway (23Atkinson K. Fogel S. Henry S.A. J. Biol. Chem. 1980; 255: 6653-6661Abstract Full Text PDF PubMed Google Scholar, 24Atkinson K.D. Jensen B. Kolat A.I. Storm E.M. Henry S.A. Fogel S. J. Bacteriol. 1980; 141: 558-564Crossref PubMed Google Scholar, 25Trotter P.J. Voelker D.R. J. Biol. Chem. 1995; 270: 6062-6070Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, 26Trotter P.J. Pedretti J. Yates R. Voelker D.R. J. Biol. Chem. 1995; 270: 6071-6080Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 27Kodaki T. Yamashita S. J. Biol. Chem. 1987; 262: 15428-15435Abstract Full Text PDF PubMed Google Scholar, 28Kodaki T. Yamashita S. Eur. J. Biochem. 1989; 185: 243-251Crossref PubMed Scopus (88) Google Scholar, 29Summers E.F. Letts V.A. McGraw P. Henry S.A. Genetics. 1988; 120: 909-922Crossref PubMed Google Scholar, 30McGraw P. Henry S.A. Genetics. 1989; 122: 317-330Crossref PubMed Google Scholar). Mutants defective in the synthesis of PS (23Atkinson K. Fogel S. Henry S.A. J. Biol. Chem. 1980; 255: 6653-6661Abstract Full Text PDF PubMed Google Scholar, 24Atkinson K.D. Jensen B. Kolat A.I. Storm E.M. Henry S.A. Fogel S. J. Bacteriol. 1980; 141: 558-564Crossref PubMed Google Scholar) and PE (25Trotter P.J. Voelker D.R. J. Biol. Chem. 1995; 270: 6062-6070Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, 26Trotter P.J. Pedretti J. Yates R. Voelker D.R. J. Biol. Chem. 1995; 270: 6071-6080Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar) can synthesize PC if they are supplemented with ethanolamine. The ethanolamine is used to synthesize PE via the CDP-ethanolamine branch of the Kennedy pathway, which is then methylated to form PC in the CDP-DAG pathway (Fig. 1) (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar). Kennedy pathway mutants (e.g. cki1 eki1 and cpt1 ept1) defective in both the CDP-choline and CDP-ethanolamine branches must synthesize PC via the CDP-DAG pathway S.C. McMaster C.R. Hjelmstad R.H. Bell R.M. J. Biol. Chem. 1994; 269: 28769-28776Abstract Full Text PDF PubMed Google Scholar, 20McMaster C.R. Bell R.M. J. Biol. Chem. 1994; 269: 28010-28016Abstract Full Text PDF PubMed Google Scholar, K. K.-H. Voelker D.R. Carman G.M. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). However, mutants defective in the CDP-DAG pathway (23Atkinson K. Fogel S. Henry S.A. J. Biol. Chem. 1980; 255: 6653-6661Abstract Full Text PDF PubMed Google Scholar, 24Atkinson K.D. Jensen B. Kolat A.I. Storm E.M. Henry S.A. Fogel S. J. Bacteriol. 1980; 141: 558-564Crossref PubMed Google Scholar, 25Trotter P.J. Voelker D.R. J. Biol. Chem. 1995; 270: 6062-6070Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, 26Trotter P.J. Pedretti J. Yates R. Voelker D.R. J. Biol. Chem. 1995; 270: 6071-6080Abstract Full Text Full Text PDF PubMed Scopus (134) Google Scholar, 27Kodaki T. Yamashita S. J. Biol. Chem. 1987; 262: 15428-15435Abstract Full Text PDF PubMed Google Scholar, 28Kodaki T. Yamashita S. Eur. J. Biochem. 1989; 185: 243-251Crossref PubMed Scopus (88) Google Scholar, 29Summers E.F. Letts V.A. McGraw P. Henry S.A. Genetics. 1988; 120: 909-922Crossref PubMed Google Scholar, 30McGraw P. Henry S.A. Genetics. 1989; 122: 317-330Crossref PubMed Google Kennedy pathway mutants not S.C. McMaster C.R. Hjelmstad R.H. Bell R.M. J. Biol. Chem. 1994; 269: 28769-28776Abstract Full Text PDF PubMed Google Scholar, K. K.-H. Voelker D.R. Carman G.M. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The synthesis of PC is with the synthesis of (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, S.A. M. Henry S.A. Biochim. Biophys. Acta. 2007; 1771: PubMed Scopus Google Scholar, G.M. Biochim. Biophys. Acta. 2007; 1771: PubMed Scopus Google Scholar). regulation is by and (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, S.A. M. Henry S.A. Biochim. Biophys. Acta. 2007; 1771: PubMed Scopus Google Scholar, G.M. Biochim. Biophys. Acta. 2007; 1771: PubMed Scopus Google Scholar, G.M. G.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, G.M. Biochem. Cell Biol. 2004; PubMed Scopus Google Scholar). In this will focus on the transcriptional regulation of glycerophospholipid synthesis glycerophospholipid synthesis are is from the growth medium and is added to the growth The by PC synthesis and is by the of choline in the growth medium F. Kohlwein S.D. Henry S.A. Jones E.W. Pringle J.R. Broach J.R. The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1992: 415-500Google Scholar, S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, G.M. Henry S.A. Rev. Biochem. 1989; PubMed Google Scholar, Rev. PubMed Google Scholar). The of glycerophospholipid synthesis is also cells the of growth and cells are of (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, G.M. Biochim. Biophys. Acta. 2007; 1771: PubMed Scopus Google Scholar). The in the and by and in the absence of (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, G.M. Biochim. Biophys. Acta. 2007; 1771: PubMed Scopus Google Scholar, P. Henry S.A. Nucleic Res. 1999; PubMed Scopus Google Scholar). The regulation of the glycerophospholipid synthesis by growth and is on the transcriptional regulatory McGraw P. Henry S.A. Nucleic Res. PubMed Scopus Google D.K. Henry S.A. J. Biol. Chem. Full Text PDF PubMed Google and M.J. Henry S.A. J. Biol. Chem. Full Text PDF PubMed Google as well as a element T. J. K. Yamashita S. J. Bacteriol. PubMed Google Scholar, Henry S.A. Nucleic Res. PubMed Scopus (100) Google Scholar, A. F. A. J. PubMed Scopus Google Scholar, K. B. R. 1995; PubMed Scopus Google Scholar) in the of the glycerophospholipid synthesis (Fig. (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, Rev. PubMed Google Scholar, J. Henry S.A. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). The element a for an that the of glycerophospholipid synthesis (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, Rev. PubMed Google Scholar, Henry S.A. Mol. Cell. Biol. PubMed Scopus Google Scholar, Henry S.A. J. Biol. Chem. 1995; 270: Full Text Full Text PDF PubMed Scopus Google Scholar, Henry S.A. Mol. Cell. Biol. PubMed Scopus Google Scholar, S. R. K. Nucleic Res. 1995; PubMed Scopus Google Scholar). of is on M.J. Henry S.A. J. Biol. Chem. Full Text PDF PubMed Google Scholar, M. B. Henry S.A. Genetics. PubMed Google which transcriptional of the by to (Fig. C. M. J. A. Mol. PubMed Scopus Google Scholar). In and mutants of mutants of F. Kohlwein S.D. Henry S.A. Jones E.W. Pringle J.R. Broach J.R. The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1992: 415-500Google Scholar, S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, G.M. Henry S.A. Rev. Biochem. 1989; PubMed Google Scholar, Rev. PubMed Google Scholar). of the of and mutants are for mutants of and it into the growth medium F. Kohlwein S.D. Henry S.A. Jones E.W. Pringle J.R. Broach J.R. The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1992: 415-500Google Scholar, S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, G.M. Henry S.A. Rev. Biochem. 1989; PubMed Google Scholar, Rev. PubMed Google Scholar). and are used as of the of and F. Kohlwein S.D. Henry S.A. Jones E.W. Pringle J.R. Broach J.R. The Molecular and Cellular Biology of the Yeast Saccharomyces: Gene Expression. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY1992: 415-500Google Scholar, S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, G.M. Henry S.A. Rev. Biochem. 1989; PubMed Google Scholar, Rev. PubMed Google Scholar). have the of to of and choline to the growth medium and for this regulation on and J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, S.A. X. M.T. Henry S.A. J. Biol. Chem. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar, S.A. P. X. M.T. Henry S.A. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus (45) Google Scholar). also major of in to and of and that to in the that are to lipid S.A. P. X. M.T. Henry S.A. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus (45) Google Scholar). that the of PA for PC synthesis the of and that the of PA the of (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar). Mutants defective in the to PC from PA via the CDP-DAG pathway (Fig. 1) in the (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, Rev. PubMed Google Scholar). the from the of which to the and of the in a CDP-DAG pathway by (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar). The of the CDP-DAG pathway mutants with the of PS from CDP-DAG can if the mutants are supplemented with a precursor that for the synthesis of glycerophospholipids via the Kennedy pathway (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar). The of the Kennedy pathway precursor also the of the in a CDP-DAG pathway (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar). of the in the CDP-DAG pathway (e.g. is H. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). However, M.J. Kohlwein S.D. M.J. Henry S.A. Carman G.M. J. Bacteriol. 1988; PubMed Google Scholar) H. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and H. W. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The of the mutants by with a Kennedy pathway will the of in (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar, 32Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (264) Google Scholar, M.J. Kohlwein S.D. M.J. Henry S.A. Carman G.M. J. Bacteriol. 1988; PubMed Google Scholar). mutants defective in the synthesis of and PC from CDP-DAG in PA and regulation of and have the to the that PA is the for (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar). In contrast, mutants defective in PC synthesis via the CDP-choline branch of the Kennedy pathway not and regulation of P. Swede M.J. Henry S.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The Kennedy pathway mutants a choline (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar). Kennedy pathway mutants that also a in the (e.g. cki1 and cpt1 choline in with an (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 9Sreenivas A. Patton-Vogt J.L. Bruno V. Griac P. Henry S.A. J. Biol. Chem. 1998; 273: 16635-16638Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar). The of choline and by mutants is on the phospholipase D-mediated turnover of PC (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 9Sreenivas A. Patton-Vogt J.L. Bruno V. Griac P. Henry S.A. J. Biol. Chem. 1998; 273: 16635-16638Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar). The that PA produced by this in the of (8Patton-Vogt J.L. Griac P. Sreenivas A. Bruno V. Dowd S. Swede M.J. Henry S.A. J. Biol. Chem. 1997; 272: 20873-20883Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 9Sreenivas A. Patton-Vogt J.L. Bruno V. Griac P. Henry S.A. J. Biol. Chem. 1998; 273: 16635-16638Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar) the that PA the for of (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar). The for generating the DAG for glycerophospholipid synthesis via the Kennedy pathway is the PA Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). that the of this the of Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar, H. J. S. S. J. 2005; PubMed Scopus Google Scholar, S. Carman G.M. S. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus (152) Google Scholar). with of and Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar, H. J. S. S. J. 2005; PubMed Scopus Google Scholar). However, the of is not to Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar, H. J. S. S. J. 2005; PubMed Scopus Google Scholar). the of the of PA that in cells Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). is by and by the H. J. S. S. J. 2005; PubMed Scopus Google Scholar). in PA S. Carman G.M. S. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus (152) Google that Cells that a are for and and require for growth S. Carman G.M. S. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus (152) Google Scholar). The that the of cells PA can by an S. Carman G.M. S. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus (152) Google Scholar) the role of in this A. T.P. J. PubMed Scopus Google Scholar, S.A. C. Henry S.A. T.P. 2004; PubMed Scopus Google Scholar, T.P. J. Biol. Chem. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar) have that the a protein M.J. Henry S.A. J. Biol. Chem. Full Text PDF PubMed Google is the membrane and the with the membrane with the membrane protein (Fig. A. T.P. J. PubMed Scopus Google Scholar). and the regulation of glycerophospholipid synthesis is mutants are for to the of J. A. K. J. Biochem. 1995; PubMed Scopus (45) Google Scholar, S. K. M. J. A. J. Bacteriol. 1998; PubMed Google Scholar, S. R. J. Biochem. PubMed Scopus Google Scholar). of the of on its with the membrane with the also in an in PC synthesis via the Kennedy pathway, and a in the Kennedy pathway (e.g. cki1 S. R. J. Biochem. PubMed Scopus Google Scholar). PC synthesis via the Kennedy pathway PA via and a in the Kennedy pathway the suppression of the of this not it is with the that PA plays a role in the regulation of and major in of glycerophospholipid synthesis regulation the that is a protein and that its with the membrane is by PA S.A. C. Henry S.A. T.P. 2004; PubMed Scopus Google Scholar). S.A. C. Henry S.A. T.P. 2004; PubMed Scopus Google Scholar) have that from the membrane into the which in a in the of PA with its as a precursor in the synthesis of via CDP-DAG (Fig. The of in response to with the of S.A. C. Henry S.A. T.P. 2004; PubMed Scopus Google Scholar). a regulatory for the of and is the of which is on the of a of PA that is required for the of the membrane S.A. C. Henry S.A. T.P. 2004; PubMed Scopus Google Scholar). The of this of the signaling role of PA by the (31Henry S.A. Patton-Vogt J.L. Prog. Nucleic Acid Res. 1998; 61: 133-179Crossref PubMed Google Scholar). in PA can by the and regulation of (e.g. CDP-DAG pathway Kennedy pathway PA and phospholipase and are to the and of this also the of is by growth and (e.g. and that PA of for the regulation of by and by is in to this is with the membrane with PA and cells are grown and in the of of essential (e.g. (Fig. cells synthesize an of M.J. A.M. Henry S.A. Carman G.M. J. Biol. Chem. 1988; Full Text PDF PubMed Google Scholar) and the of PA the membrane (Fig. S.A. C. Henry S.A. T.P. 2004; PubMed Scopus Google Scholar). the in an in PA Carman G.M. J. Bacteriol. 1988; PubMed Google which to the in the PA TAG is synthesized the of glycerophospholipids in cells Biochim. Biophys. Acta. PubMed Scopus Google and PA is this growth K. Yamashita S. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). The PA plays a major role in TAG and its in the PA Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). In cells, synthesis Carman G.M. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google and this the PA The in synthesis in response to is not the of of is this growth Carman G.M. J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). the in synthesis is to the of Carman G.M. J. Biol. Chem. 2005; Full Text Full Text PDF PubMed Scopus Google Scholar). PA W. M. of in Saccharomyces cerevisiae by and this the PA regardless of whether cells are supplemented with are of an essential a in the PA in of with the by into the In the of the glycerophospholipid synthesis that are its with The of (e.g. CDP-DAG PA and phospholipase that to the PA the membrane have a major on glycerophospholipid synthesis regulation by the of PA plays a role in the regulation of and S. Carman G.M. S. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus (152) Google Scholar). However, it is growth (e.g. and the of the is by protein A. Carman G.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google protein A. M.J. Henry S.A. Carman G.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google and Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google Scholar). by protein and function A. Carman G.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, Carman G.M. J. Biol. Chem. 2006; Full Text Full Text PDF PubMed Scopus Google by protein function A. M.J. Henry S.A. Carman G.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the of with is in with in major signaling pathways that the protein response J. Yamashita S. Mol. PubMed Scopus Google Scholar, P. Cell. Full Text PDF PubMed Scopus Google Scholar, S.A. Henry S.A. Genetics. 2004; PubMed Scopus Google the protein protein pathway R. in The of the and the response pathway Patton-Vogt J. A. Kohlwein S.D. Henry S.A. Mol. Cell. Biol. PubMed Scopus Google Scholar). have to the that signaling pathways a role in the The that into the in response to PA is the major for of that signaling pathways must a roles of by as for protein A. M.J. Henry S.A. Carman G.M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google by and the as for the response pathway R. R. PubMed Scopus Google Scholar, Henry J. 2005; PubMed Scopus Google Scholar). However, on the of and mutants defective in the response pathway can by of the of Patton-Vogt J. A. Kohlwein S.D. Henry S.A. Mol. Cell. Biol. PubMed Scopus Google the the in acid synthesis. is a of to mammalian protein in both yeast and A. J. X. M. J. Biol. Chem. 1994; 269: Full Text PDF PubMed Google Scholar). from acid synthesis also is that are also the de novo synthesis of PA as on the of lipid with as membrane trafficking and to stress and via the major signaling pathways into the roles of PA in the of regulation and lipid signaling in both and We M. A. and J. for on the
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