George M. Carman Professor Rutgers University Dept. of Food Science Food Science Bldg.- Room 203E School of Environ & Biol Sciences New Brunswick. NJ 08901 (732) 932-9611. Ext. 217 FAX- 6776 carman@aesop.rutgers.edu Visit Dr's Carman's webpage

Regulation of phospholipid metabolism. signaling in yeast

Dr. George M. Carman is a Professor of Food Science at Rutgers University. He received his Ph.D. degree from the University of Massachusetts. and postdoctoral training at the University of Texas Medical School in Houston. Dr. Carman's research utilizes molecular genetic and biochemical approaches to study the regulation of phospholipid metabolism in the yeast Saccharomyces cerevisiae. Phospholipids are essential molecules that contribute to the structural definition of cell membranes. and participate in the regulation of cellular processes as signaling molecules and as reservoirs of lipid messengers. The Carman laboratory has made significant contributions to the understanding of phospholipid synthesis in yeast through the purification and characterization of several enzymes and the isolation and characterization of key genes. The laboratory has played a major role in the discovery that the expression of phospholipid biosynthetic enzymes is regulated by phospholipid precursors and the mineral zinc; and that key enzymes are regulated by membrane- and cytosolic-associated components and by covalent modification by protein kinases. These forms of enzyme regulation have profound effects on membrane phospholipid composition and have important medical implications for understanding the molecular basis for various diseases. Two research projects are currently funded by grants from the National Institutes of Health. One project addresses the hypothesis that phosphorylation of phospholipid biosynthetic enzymes represents a mechanism by which pathways of signal transduction mediate phospholipid metabolism. Key enzymes being studied include choline kinase and CTP synthetase. Unregulated levels of these two enzymes are common properties of various cancers in humans. The other project addresses the hypothesis that yeast cells adapt to zinc deficiency by regulating membrane phospholipid synthesis through the expression of several phospholipid biosynthetic enzymes. Key enzymes being studied include phosphatidylserine synthase. phosphatidylinositol synthase. and phosphatidate phosphatase.

Dr. Carman is a Fellow of the American Academy of Microbiology. and is the recipient of the AOAC-Supelco/Nicholas Pelick Research Award. Selman A. Waksman Honorary Lectureship Award. the Rutgers University Board of Trustees Award for Excellence in Research. and the New Jersey Agricultural Experiment Station Research Excellence Award. He is a former chair and organizer of the Gordon Research Conference on Lipid Metabolism and the Keystone Symposium on Lipid Second Messengers. and served as chair of the American Society for Biochemistry and Molecular Biology (ASBMB) Program Planning Committee and the ASBMB Meetings Committee. He served as President of the Theobald Smith Society. the New Jersey branch of the American Society for Microbiology. and served on the Journal of Biological Chemistry editorial board and Physiological Chemistry Study Section of the National Institutes of Health. Dr. Carman currently serves as an Executive Editor for Analytical Biochemistry and Biochimica et Biophysica Acta. and as Associate Editor of the Journal of Lipid Research.

Selected Publications

Soto, A., and Carman, G.M.  (2008).  Regulation of the Saccharomyces cerevisiae CKI1-encoded choline kinase by zinc depletion. J. Biol. Chem. 283: 10079-10088.

Havriluk, T., Lozy, F., Siniossoglou, S. and Carman, G.M.  (2008).  Colorimetric determination of pure Mg2+-dependent phosphatidate phosphatase activity.  Anal. Biochem.  373: 392-394.

Han, G.-S., Siniossoglou, S. and Carman, G.M.  (2007).  The cellular functions of the yeast lipin homolog Pah1p are dependent on its phosphatidate phosphatase activity.  J. Biol. Chem. 282: 37026-37035.

Choi, H.-S., and Carman, G.M. ( 2007). Respiratory deficiency mediates the regulation of CHO1-encoded phosphatidylserine synthase by mRNA stability in Saccharomyces cerevisiae. J. Biol. Chem. 282: 31217-31227.

Chang YF, Martin SS, Baldwin EP, Carman GM. (2007) Phosphorylation of human CTP synthetase 1 by protein kinase C: identification of Ser462 and Thr455 as major sites of phosphorylation. J. Biol. Chem. 282: 17613-17622.

Choi MG, Carman GM. (2007) Phosphorylation of human CTP synthetase 1 by protein kinase A: identification of Thr455 as a major site of phosphorylation. J Biol Chem. 282(8):5367-77.

Carman GM, Henry SA. (2007) Special issue: Regulation of lipid metabolism in yeast. Biochim Biophys Acta. 1771(3):239-40.

Carman GM, Han GS. (2007) Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc depletion. Biochim Biophys Acta. 1771(3):322-30.

Kersting MC. Carman GM. (2006) Regulation of the Saccharomyces cerevisiae EKI1-encoded ethanolamine kinase by zinc depletion. J Biol Chem. 281(19):13110-6.

Han GS. Wu WI. Carman GM. (2006) The Saccharomyces cerevisiae Lipin homolog is a Mg2+-dependent phosphatidate phosphatase enzyme. J Biol Chem. 281(14):9210-8.

Chang YF. Carman GM. (2006) Casein kinase II phosphorylation of the yeast phospholipid synthesis transcription factor Opi1p. J Biol Chem. 281(8):4754-61.

Chang FS. Han GS. Carman GM. Blumer KJ. (2005) A WASp-binding type II phosphatidylinositol 4-kinase required for actin polymerization-driven endosome motility. J Cell Biol. 171(1):133-42.

Han GS. Sreenivas A. Choi MG. Chang YF. Martin SS. Baldwin EP. Carman GM. (2005) Expression of Human CTP synthetase in Saccharomyces cerevisiae reveals phosphorylation by protein kinase A. J Biol Chem. 280(46):38328-36.

Han SH. Han GS. Iwanyshyn WM. Carman GM. (2005) Regulation of the PIS1-encoded phosphatidylinositol synthase in Saccharomyces cerevisiae by zinc. J Biol Chem. 280(32):29017-24.

Choi. M.-G.. Kurnov. V.. Kersting. M.C.. Sreenivas. A.and Carman. G.M. (2005) Phosphorylation of the yeast choline kinase by protein kinase C. Identification of Ser25 and Ser30 as major sites of phosphorylation. J. Biol. Chem. 280: 26105-26112.

Kersting. M.C.. Choi. H.-S. and Carman. G.M. (2004). Regulation of the yeast EKI1-encoded ethanolamine kinase by inositol and choline. J. Biol. Chem. 279: 35353-35359.

Iwanyshyn. W.M.. Han. G.-S. and Carman. G.M. (2004). Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc. J. Biol. Chem. 279: in press.

Choi. H.-S.. Sreenivas. A.. Han. G.-S. and Carman. G.M. (2004). Regulation of phospholipid synthesis in the yeast cki1D eki1D mutant defective in the Kennedy pathway. The CHO1-encoded phosphatidylserine synthase is regulated by mRNA stability. J. Biol. Chem. 279: 12081-12087.

Han. G.-S.. Johnston. C.N. and Carman. G.M. (2004). Vacuole membrane topography of the DPP1-encoded diacylglycerol pyrophosphate phosphatase catalytic site from Saccharomyces cerevisiae. J. Biol. Chem. 279: 5338-5345.

Oshiro. J.. Han. G.-S.. Iwanyshyn. W.M.. Conover. K. and Carman. G.M. (2003). Regulation of the yeast DPP1-encoded diacylglycerol pyrophosphate phosphatase by transcription factor Gis1p.J. Biol. Chem. 278: 31495-31503.

Choi. M.-G.. Park. T.-S. and Carman. G.M. (2003). Phosphorylation of Saccharomyces cerevisiae CTP synthetase at Ser⁴²⁴ by protein kinases A and C regulates phosphatidylcholine synthesis by the CDP-choline pathway.J. Biol. Chem. 278: 23610-23616.

Sreenivas. A.. and Carman. G.M. (2003). Phosphorylation of the yeast phospholipid synthesis regulatory protein Opi1p by protein kinase A.J. Biol. Chem. 278: 20673-20680.