CTP:Phosphocholine Cytidylyltransferase: Paving the Way from Gene to Membrane

PC 1The abbreviations used are: PC, phosphatidylcholine; CCT, also known as CT, CTP:phosphocholine cytidylyltransferase; CSF-1, colony-stimulating factor 1; DSPC, disaturated phosphatidylcholine; G3PCT, CTP:glycerol-3-phosphate cytidylyltransferase; GroPCho, glycerol-3-phosphocholine; HDL, high density lipoprotein; LDL, low density lipoprotein; NLS, nuclear localization sequence; NTE, neuropathy target esterase; PEMT, phosphatidylethanolamine N-methyltransferase; PE, phosphatidylethanolamine; PI, phosphatidylinositol; VLDL, very low density lipoprotein. is the most abundant phospholipid in eukaryotic membranes whereas few prokaryotes contain PC. PC is synthesized in eukaryotes by two routes: the CDP-choline pathway (1Kent C. Biochim. Biophys. Acta. 1997; 1348: 79-90Crossref PubMed Scopus (182) Google Scholar) and PE methylation (2Vance J.E. Vance D.E. Biochem. Cell Biol. 2004; 82: 113-128Crossref PubMed Scopus (247) Google Scholar). PE methylation is the most important contributor to PC formation in Saccharomyces cerevisiae (3Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (251) Google Scholar). In contrast, mammalian cells and tissues predominantly use the CDP-choline pathway (2Vance J.E. Vance D.E. Biochem. Cell Biol. 2004; 82: 113-128Crossref PubMed Scopus (247) Google Scholar, 4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar). PC is the major phospholipid in plant extraplastid membranes, and the CDP-choline pathway operates in Brassica napus (5Nishida I. Swinhoe R. Slabas A.R. Murata N. Plant Mol. Biol. 1996; 31: 205-211Crossref PubMed Google Scholar), Arabidopsis thaliana (6Choi S.B. Lee K.W. Cho S.H. Mol. Cell. 1997; 7: 58-63Google Scholar, 7Inatsugi R. Nakamura M. Nishida I. Plant Cell Physiol. 2002; 43: 1342-1350Crossref PubMed Google Scholar), and Pisum sativum (8Jones P.L. Willey D.L. Gacesa P. Harwood J.L. Plant Mol. Biol. 1998; 37: 179-185Crossref PubMed Scopus (9) Google Scholar). PC is present in select prokaryotes, including Treponema denticola, whose genome encodes a fusion protein containing both choline kinase and CCT activities (9Kent C. Gee P. Lee S.Y. Bian X. Fenno J.C. Mol. Microbiol. 2004; 51: 471-481Crossref PubMed Scopus (29) Google Scholar). On the other hand, Sinorhizobium meliloti produces PC by the condensation of choline and CDP-diacylglycerol catalyzed by the novel PC synthase (10Sohlenkamp C. Lopez-Lara I.M. Geiger O. Prog. Lipid Res. 2003; 42: 115-162Crossref PubMed Scopus (202) Google Scholar). The CCTs in bacteria do not resemble any of the other known CCTs (11Campbell H.A. Kent C. Biochim. Biophys. Acta. 2001; 1534: 85-95Crossref PubMed Scopus (19) Google Scholar, 12Kwak B.Y. Zhang Y-M. Yun M. Heath R.J. Rock C.O. Jackowski S. Park H.W. J. Biol. Chem. 2002; 277: 4343-4350Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar, 13Rock C.O. Heath R.J. Park H-W. Jackowski S. J. Bacteriol. 2001; 183: 4927-4931Crossref PubMed Scopus (27) Google Scholar). There are three steps in the CDP-choline pathway. Choline is an essential nutrient in mammals and is transported into the cell and phosphorylated by choline kinase. CCT catalyzes the condensation of CTP and phosphocholine to form CDP-choline, which in turn donates the phosphocholine moiety to diacylglycerol to form PC. CCT mediates the rate-limiting step in this pathway (1Kent C. Biochim. Biophys. Acta. 1997; 1348: 79-90Crossref PubMed Scopus (182) Google Scholar) and is unique in that its enzymatic activity is regulated by association with membrane structures (14Cornell R.B. Northwood I.C. Trends Biochem. Sci. 2000; 25: 441-447Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar, 15Johnson J.E. Cornell R.B. Mol. Membr. Biol. 1999; 16: 217-235Crossref PubMed Scopus (222) Google Scholar). A current model posits that bilayer curvature elastic stress is sensed by CCT and governs the degree of membrane association, thus providing a mechanism for both positive and negative regulation of activity (16Attard G.S. Templer R.H. Smith W.S. Hunt A.N. Jackowski S. Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 9032-9036Crossref PubMed Google Scholar, 17Davies S.M. Epand R.M. Kraayenhof R. Cornell R.B. Biochemistry. 2001; 40: 10522-10531Crossref PubMed Scopus (106) Google Scholar). The PEMT is the only enzyme in the alternative pathway, and it performs all three of the methylation steps. The significance of PE methylation to PC production is controlled by the expression of PEMT, which is high in liver and testis (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar, 18Jacobs R.L. Devlin C. Tabas I. Vance D.E. J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). The goal of this minireview is to highlight recent progress in understanding the regulation of CCT expression and a growing appreciation of its role in cell biology and organ function. The regulatory biochemistry of CCT is discussed in several recent reviews (1Kent C. Biochim. Biophys. Acta. 1997; 1348: 79-90Crossref PubMed Scopus (182) Google Scholar, 2Vance J.E. Vance D.E. Biochem. Cell Biol. 2004; 82: 113-128Crossref PubMed Scopus (247) Google Scholar, 14Cornell R.B. Northwood I.C. Trends Biochem. Sci. 2000; 25: 441-447Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar, 15Johnson J.E. Cornell R.B. Mol. Membr. Biol. 1999; 16: 217-235Crossref PubMed Scopus (222) Google Scholar, 19Lykidis A. Jackowski S. Prog. Nucleic Acids Res. Mol. Biol. 2000; 65: 361-393Crossref Google Scholar, 20Jackowski S. Baburina I. Templer R.H. Leatherbarrow R. Probing and Modeling Membranes and Proteins. Royal Society of Chemistry, London, UK2002: 163-176Google Scholar, 21Jackowski S. Haldar D. Das S.K. Glycerolipid Metabolizing Enzymes. Research Signpost, Trivandrum, India2002: 109-124Google Scholar, 22Clement J.M. Kent C. Biochem. Biophys. Res. Commun. 1999; 257: 643-650Crossref PubMed Scopus (53) Google Scholar). The mammalian CCT proteins are divided into four functional domains. The N-terminal domains are distinct and either contain a nuclear localization signal (CCTα) or not (CCTβ). The catalytic domain contains two motifs, HXGH and of the P. C. PubMed Scopus Google Scholar), which are in CTP Cornell R.B. Biochemistry. 1996; PubMed Scopus (27) Google Scholar, Kent C. Biochemistry. 2003; 42: PubMed Scopus Google Scholar). A the CTP is in phosphocholine Kent C. Biochemistry. 2003; 42: PubMed Scopus Google Scholar). CCT is a H.A. Kent C. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, M. Smith J.L. Zhang D. Cornell R.B. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar). The high of the a role for in the catalytic mechanism of the CCT protein S. Kent C. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, S.Y. S. Kent C. Biol. 2001; PubMed Scopus Google Scholar, S. H.A. Kent C. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Google Scholar, Park S. Kent C. 1999; 7: Full Text Full Text PDF Scopus Google Scholar). in the CCTs and J.M. Kent C. Biochem. Biophys. Res. Commun. 1999; 257: 643-650Crossref PubMed Scopus (53) Google Scholar, Biochim. Acta. 2004; PubMed Scopus Google Scholar) a major role in the and regulation of the enzyme (1Kent C. Biochim. Biophys. Acta. 1997; 1348: 79-90Crossref PubMed Scopus (182) Google Scholar, 14Cornell R.B. Northwood I.C. Trends Biochem. Sci. 2000; 25: 441-447Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar, 15Johnson J.E. Cornell R.B. Mol. Membr. Biol. 1999; 16: 217-235Crossref PubMed Scopus (222) Google Scholar, 19Lykidis A. Jackowski S. Prog. Nucleic Acids Res. Mol. Biol. 2000; 65: 361-393Crossref Google Scholar, Biochim. Acta. 2004; PubMed Scopus Google Scholar). The or domain with both and and is the of the protein that to the bilayer curvature elastic stress (6Choi S.B. Lee K.W. Cho S.H. Mol. Cell. 1997; 7: 58-63Google Scholar, 14Cornell R.B. Northwood I.C. Trends Biochem. Sci. 2000; 25: 441-447Abstract Full Text Full Text PDF PubMed Scopus (174) Google Scholar, M. Smith J.L. Zhang D. Cornell R.B. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar, J.E. M. R. Cornell R.B. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, S. J.E. Cornell R.B. Biochemistry. 2003; 42: PubMed Scopus Google Scholar). of the in an enzyme that catalytic activity high CTP to regulation H.A. Kent C. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, A. Jackson P. Jackowski S. Biochemistry. 2001; 40: PubMed Scopus Google Scholar). The or the domain in mammalian the enzyme in to the domain is A. Jackson P. Jackowski S. Biochemistry. 2001; 40: PubMed Scopus Google Scholar). The CCTs of eukaryotes do not a domain to the domain are J.M. Kent C. Biochem. Biophys. Res. Commun. 1999; 257: 643-650Crossref PubMed Scopus (53) Google Scholar). of CCTs S. cerevisiae J.E. S. Cornell R.B. Biochem. J. PubMed Scopus (45) Google Scholar, Park Kent C. 2001; PubMed Scopus Google Scholar), Biochem. J. 1997; PubMed Scopus Google Scholar), and Kent C. Biochim. Biophys. Acta. 2001; PubMed Scopus Google Scholar). is of a that with membrane and the protein with catalytic The mammalian CCTs are phosphorylated of the domain (1Kent C. Biochim. Biophys. Acta. 1997; 1348: 79-90Crossref PubMed Scopus (182) Google Scholar). CCT to select Cornell R.B. Biochemistry. 1997; PubMed Scopus Google Scholar) and activity Cornell R.B. Biochemistry. 1997; PubMed Scopus Google Scholar, R.B. R.J. M.A. Biochem. J. PubMed Google Scholar). of CCT membrane association in or cells or in localization not a and the of CCT activity in with the that is a mechanism for M. C. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, M. PubMed Scopus Google Scholar) to the enzyme activity in to membrane The CCT protein is two distinct in and encodes the Tabas I. J. Biol. Chem. 1997; Full Text Full Text PDF PubMed Scopus Google Scholar, M.A. Jackson P. Jackowski S. Biochim. Biophys. Acta. 2003; PubMed Scopus Google Scholar), and encodes the and M.A. Jackson P. Jackowski S. Biochim. Biophys. Acta. 2003; PubMed Scopus Google Scholar, A. Baburina I. Jackowski S. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, A. Jackowski S. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). is in and is in both CCT activity is the of and and any of the four protein a cell M.A. Jackson P. Jackowski S. Biochim. Biophys. Acta. 2003; PubMed Scopus Google Scholar, A. Baburina I. Jackowski S. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, A. Jackowski S. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar). The and proteins are in the catalytic and domains both is in the with membranes, the is in the as by the N-terminal nuclear localization In contrast, the A. Baburina I. Jackowski S. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). is with and a nuclear CDP-choline pathway is in or A.N. G.S. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). is with the of PC the CDP-choline pathway in liver J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar) that nuclear CCT in PC nuclear is also of as a for a to an PC as the membrane with I.C. Cornell R.B. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar), or of membrane to of PC Miller Mol. Cell. Biol. 2002; PubMed Scopus Google Scholar). are and are not The of protein is the with R. M. J. Physiol. 2004; PubMed Scopus Google Scholar) in cells and tissues R. I. Wang J. M. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, I. R. J. Wang J. M. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar), which a high for PC or that the CCT in Cell that the pathway regulated by CCT a role in providing PC for cell the of a cell CCT activity Proc. Natl. Acad. Sci. U. S. A. PubMed Scopus Google Scholar, M. Proc. Natl. Acad. Sci. U. S. A. PubMed Google Scholar). The to PC by the PEMT this CCT Vance D.E. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar), and PEMT is not in liver and testis (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar, 18Jacobs R.L. Devlin C. Tabas I. Vance D.E. J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). The of CCT to and to membrane in several to is by an of PC and an in to in a cell that is for both and Rock C.O. Cornell R.B. Jackowski S. J. Biol. Chem. Full Text PDF PubMed Google Scholar). the of protein is and the and the signal CCT protein and the and to the cell S. Baburina I. Templer R.H. Leatherbarrow R. Probing and Modeling Membranes and Proteins. Royal Society of Chemistry, London, UK2002: 163-176Google Scholar). The of to cells in of PC into and is by CCT activity all of the CCT protein is in the and I. R. J. Wang J. M. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar). In which are for not CCT protein expression is and a of the nuclear protein to membrane I.C. Cornell R.B. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). On the other hand, of is not by an in PC in or I. R. J. Wang J. M. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar). the the that and PC is either by expression or by The of the cell I. R. J. Wang J. M. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar, J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, M. Vance D.E. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). PC the CCT activity I. R. J. Wang J. M. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar, M. Vance D.E. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, S. J. Biol. Chem. Full Text PDF PubMed Google Scholar, Vance D.E. J. Lipid Res. Full Text PDF PubMed Google Scholar), and the CCT activity the cell I. R. J. Wang J. M. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar, M. Vance D.E. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, S. J. Biol. Chem. Full Text PDF PubMed Google Scholar) it is by of the the to and I. R. J. Wang J. M. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar, S. J. Biol. Chem. Full Text PDF PubMed Google Scholar). is the the J. J. Lipid Res. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar) and C. Vance D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar) of the factor to the M. Vance D.E. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar) in for cell The of PC is not controlled by the expression of PC is in PC the cell S. J. Biol. Chem. Full Text PDF PubMed Google Scholar). is and to PC and membrane formation with the of and the membrane is with it is of S. J. Biol. Chem. Full Text PDF PubMed Google Scholar), that of do not phospholipid and thus used to membrane In CCT is the the pathway the of PC not Cornell R.B. J. Biol. Chem. Full Text PDF PubMed Google Scholar, I. Jackowski S. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). is to the of PC and the formation of Cornell R.B. J. Biol. Chem. Full Text PDF PubMed Google Scholar, I. Jackowski S. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar). The enzyme is to the I. Jackowski S. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar, A. Biochim. Biophys. Acta. 1999; PubMed Scopus Google Scholar) the O. D. P. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar). of which is by choline and into CDP-choline, a with On the other hand, of not PC the as as and Jackowski S. Biochem. Biophys. Res. Commun. 2001; PubMed Scopus Google Scholar), which and CCT in and it is a target in the by other PC is essential not only for cell and also for cell M. Biochim. Biophys. Acta. 2002; PubMed Scopus Google Scholar). of PC to either a in CCT M. M. Vance D.E. J. Biol. Chem. 1996; Full Text Full Text PDF PubMed Scopus Google Scholar, M. Biochem. J. 2003; 643-650Crossref PubMed Google Scholar), of CCT activity A. Jackowski S. Prog. Nucleic Acids Res. Mol. Biol. 2000; 65: 361-393Crossref Google Scholar, M. P. M. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar, M. Jackowski S. Mol. 2002; PubMed Scopus (29) Google Scholar, D. Biochem. J. 2000; PubMed Google Scholar, M. M. J. Biochem. 1999; PubMed Scopus Google Scholar, I. Jackowski S. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), or J. Jackowski S. Smith S.H. J. 2004; PubMed Scopus Google Scholar) to cell by or a that of both and J.M. Jackowski S. Mol. 2003; PubMed Scopus Google Scholar). in PC Miller Mol. Cell. Biol. 2002; PubMed Scopus Google Scholar, J.M. Jackowski S. Mol. 2003; PubMed Scopus Google Scholar) and the protein a stress M. Biochem. J. 2003; 643-650Crossref PubMed Google Scholar). the to PC, the and a target for of the N-terminal Miller Mol. Cell. Biol. 2002; PubMed Scopus Google Scholar). The of protein the is with CCT a that operates cell by other as factor S. Biochim. Biophys. Acta. 1998; PubMed Scopus Google Scholar). the of CCT is in the is in cells J. J. J. Cell Mol. Biol. 2004; PubMed Scopus Google Scholar) is a high with other tissues (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar). The and with three in the M. Vance D.E. J. Lipid Res. 2000; Full Text Full Text PDF PubMed Google Scholar). expression the cell J. J. Lipid Res. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar, C. Vance D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), and mediates expression in by the kinase M. K. Vance D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). expression either by of its to the or by with S. K. M. Vance D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar, M. S. Vance D.E. J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). Lipid J. Lipid Res. 2000; Full Text Full Text PDF PubMed Google Scholar), and of activity that a in the governs this J. J. Lipid Res. 2001; 42: Full Text Full Text PDF PubMed Google Scholar, J.L. Biochem. J. 2002; PubMed Google Scholar). and activity are are to the and in of activity in cell with protein that the regulation of and the CDP-choline pathway J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar) to the of CCT expression by or and activity by expression of membranes J.M. R.B. Vance J.E. Vance D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), is known the and the that to the expression of and is not in (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar) and an in distinct CCT are in A. and expression in to R. Nakamura M. Nishida I. Plant Cell Physiol. 2002; 43: 1342-1350Crossref PubMed Google Scholar, M. P.L. Plant Physiol. PubMed Scopus Google Scholar). A and a are in the Lee Cho S.H. Mol. Cell. 2001; Scholar). The the regulation of CCT is in its and in this CCT expression to and CCT in the and expression are in to other tissues are The of and of cells (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar, J.M. R.B. Vance J.E. Vance D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar), to the in expression is in with the Wang 2000; PubMed Scopus Google Scholar). with are to CCT cells which CCT and PC J. D. C. S. J. 2002; 16: PubMed Scopus Google Scholar). In an of is with CCT activity and PC in the R. J. K. J. 2004; PubMed Scopus Google Scholar). In both PC to the R. J. Res. 2002; PubMed Scopus Google Scholar). in CCT activity the of the diacylglycerol not only the of membrane PC also the of in an Vance D.E. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, S. Wang J. Baburina I. Biochim. Biophys. Acta. 2000; PubMed Scopus Google Scholar). PC also as by the of the in formation PC formation is J.M. J. Lipid Res. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). The expression of in the that it a in this the do not a (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar). CCT in the a regulatory role in the production of DSPC, a major into the of protein expression M. M. Lee M. Biochem. J. 1996; PubMed Scopus Google Scholar), of cells CCT activity M. M. Lee M. Biochem. J. 1996; PubMed Scopus Google Scholar, Biochem. J. 1996; PubMed Google Scholar), and both are by CCT activity a of in to factor Jackowski S. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar) or J. J. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar) both the and the regulatory domains of the protein and Biochem. J. 1996; PubMed Google Scholar, J. Smith D. R.J. J. Physiol. 2001; Scholar, S. J. Smith D. R.J. J. Physiol. 2001; Scholar) or M. J. Cell. Physiol. PubMed Scopus Google Scholar, R.J. Zhang M. S. J. 2003; PubMed Scopus Google Scholar) the membrane and the membrane association of an of CCT Biochem. J. 1996; PubMed Google Scholar, Cornell R.B. J. Biol. Chem. Full Text PDF PubMed Google Scholar), and also expression in cells by a mechanism that is a negative regulatory in the K. Biochem. J. 2004; PubMed Scopus Google Scholar). is to CCT J. Smith D. R.J. J. Physiol. 2001; Scholar, S. J. Smith D. R.J. J. Physiol. 2001; Scholar, J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar), an in a mechanism M. Jackowski S. Mol. 2002; PubMed Scopus (29) Google Scholar). In contrast, the are of CCT activity of to M. Jackowski S. Mol. 2002; PubMed Scopus (29) Google Scholar, S. J. Smith D. R.J. J. Physiol. 2001; Scholar, Rock C.O. Jackowski S. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). CCT in the PC in the liver is by and the PEMT (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar). The expression of is to liver and in that PEMT R. Vance D.E. Proc. Natl. Acad. Sci. U. S. A. 1997; PubMed Google Scholar), the X. J. S.H. Biochem. J. 2003; PubMed Scopus Google Scholar). A and this with the CDP-choline pathway A. Vance D.E. Vance J.E. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar), that CCT expression to PC. and of liver PEMT (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar), that is a in the In the of PEMT, only an of and PC to a high HDL, Vance D.E. J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). are with the that PC the CDP-choline pathway also to R.L. Devlin C. Tabas I. Vance D.E. J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar, Vance D.E. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). The of a PC by the PEMT is by the localization of PEMT to the membrane it of PC Wang R. S. Vance D.E. M. J.L. J. Lipid Res. 2003; Full Text Full Text PDF PubMed Scopus (37) Google Scholar). The that and PEMT and that it is a in the for PC production that an liver function. to the of CCT in mammalian CCT is for cell in the of expression to to the of to D. C. Jackowski S. Tabas I. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus (53) Google Scholar). expression is in is is to expression to D. C. Jackowski S. Tabas I. J. Biol. Chem. 2000; Full Text Full Text PDF PubMed Scopus (53) Google Scholar). the to is of CCT in cell in expression is in PEMT, which is a very contributor to PC in this is in R.L. Devlin C. Tabas I. Vance D.E. J. Biol. Chem. 2004; 279: 47402-47410Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar). PC as as HDL, LDL, and the liver are that CCT and the CDP-choline pathway do an important role in of and with the PEMT to Vance D.E. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). of activity in the and of in only a in J. J. Cell Mol. Biol. 2002; PubMed Scopus Google Scholar). expression of CCT is with regulation and PC Cornell R.B. J. Biol. Chem. Full Text PDF PubMed Google Scholar, I. Jackowski S. J. Biol. Chem. 1999; Full Text Full Text PDF PubMed Scopus Google Scholar) that in by O. D. P. J. Biol. Chem. 2004; 279: Full Text Full Text PDF PubMed Scopus Google Scholar). of expression in a to and a in and the (4Jackowski S. Rehg J.E. Zhang Y-M. Wang J. Miller K. Jackson P. Karim M.A. Mol. Cell. Biol. 2004; 24: 4720-4733Crossref PubMed Scopus (45) Google Scholar). that the of expression is in The a to is that the is in this of of the two CCT in D. in a and are 2003; PubMed Scopus (37) Google Scholar). is to membrane of and factor U. C. M. Cell. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). a role for the in to a and to the for this The that in that is 2003; PubMed Scopus (37) Google Scholar). The association of the CDP-choline pathway with in (3Carman G.M. Henry S.A. Prog. Lipid Res. 1999; 38: 361-399Crossref PubMed Scopus (251) Google Scholar, 2000; PubMed Google Scholar, Cell Biol. 2003; PubMed Scopus Google Scholar, M. Mol. Biol. Cell. 2001; PubMed Google Scholar) that CCT activity a in mammalian CCT is a in membrane phospholipid a and in the that not the of CCT is is to PC CCT activity is regulated a its with membrane and and to a of and There is that CCT with of CCT are and to of which to the known the of the CCTs into a CCT a a mechanism for cell are also of the CCT that are to is to in the enzyme activity in cell not its activity in cells of the regulation by the membrane the of and the of that the to the of CCT in and to the to understanding the of