SUZANNE JACKOWSKI
ASSOCIATE PROFESSOR

EDUCATION:
B.A. 1972, Canisius College, Buffalo, New York
Ph.D. 1977, University of Tennessee at Oak Ridge, Tennessee

RESEARCH INTERESTS: The long-term goal is to define the mechanisms that regulate membrane phospholipid biosynthesis and catabolism. Phospholipid production is coordinated with DNA synthesis and the cell cycle to provide the cell with a precisely balanced membrane composition. The key rate-determining step in membrane phospholipid biogenesis is CTP:phosphocholine cytidylyltransferase. This enzyme is activated by its association with membranes and regulated by phosphorylation. Growth factors control the amount of protein by regulating the levels of cytidylyltransferase mRNA. The accumulation of membrane occurs during S phase of the cell cycle and results from periodic oscillations in the activities of the cytidylyltransferase and of phospholipase degradation. Current work focuses on characterizing the attenuation of cytidylyltransferase activity by phosphorylation of specific serine residue(s) by the cyclin kinases during G2/M phases. Degradation of membrame phosphatidylcholine by phospholipases ceases during S phase and the nature of this metabolic switch leading to the doubling of cellular phospholipid is under investigation. Candidate enzymes include the macrophage 85 kDa cytosolic phospholipase A2 and the phospholipase C which is mitogenic in this cell type. Approaches to these problems include site-directed mutagenesis and heterologous expression of cytidylyltransferase protein, characterization of enzyme activity, and transfection of target genes into macrophages followed by cell cycle analysis and metabolic evaluation of membrane formation.

CURRENT RESEARCH SUPPORT:
NIGMS 1 RO1 GM45737 "Regulation of membrane biosynthesis by CSF-1" April 1, 1995 - March 31, 2001; $749,074.

GRADUATE STUDENTS:
The University of Tennessee, Memphis: Woojoo Song, 1989 -1993.

PUBLICATIONS: (Only selected publications appearing since 1992 are listed.)
37. Rock, C.O., Cleveland, J.L. and Jackowski, S. (1992) Macrophage growth arrest by cAMP defines a distinct checkpoint in the mid-G1 stage of the cell cycle and overrides constitutive c-myc expression. Mol. Cell.Biol., 12, 2351-2358.
38. Song, W-J. and Jackowski, S. (1992) Cloning, sequencing and expression of the pantothenate kinase (coaA) gene of Escherichia coli. J. Bacteriol., 174, 6411-6417.
39. Luche, M.M., Rock, C.O., and Jackowski, S. (1993) Expression of rat CTP:phosphocholine cytidylyltransferase in insect cells using a baculovirus vector. Arch. Biochem. Biophys., 301, 114-118.
40. Xu, X-X., Tessner, T.G., Rock, C.O., and Jackowski, S. (1993) Phosphatidylcholine hydrolysis and c-myc expression are in collaborating mitogenic pathways activated by colony-stimulating factor 1. Mol. Cell. Biol., 13, 1522-1533.
41. Furukawa, H., Tsay, J-T., Jackowski, S., Takamura, Y., and Rock, C.O. (1993) Thiolactomycin resistance in Escherichia coli is associated with the multidrug resistance efflux pump encoded by emrAB. J. Bacteriol., 175, 3723-3729.

42. Rutherford, M.S., Rock, C.O., Jenkins, N.A., Gilbert, D.J., Tessner, T.G., Copeland, N.G., and Jackowski, S. (1993) The gene for murine CTP:phosphocholine cytidylyltransferase (Ctpct) is located on mouse chromosome 16. Genomics, 18, 698-701.
43. Jackowski, S., Jackson, P.D., and Rock, C.O. (1994) Sequence and function of the aas gene in Escherichia coli. J. Biol. Chem., 269, 2921-2928.
44. Jackowski S. (1994) Coordination of membrane phospholipid synthesis with the cell cycle.
J. Biol. Chem., in press.
45.Heath, R.J., Jackowski, S., and Rock, C.O. (1994) Guanosine tetraphosphate inhibition of fatty acid and phospholipid synthesis in Escherichia coli is relieved by overexpression of glycerol-3-phosphate acyltransferase (plsB). J. Biol. Chem., 269, 26584-26590.
46.Song, W-J. and Jackowski, S. (1994) Kinetics and regulation of pantothenate kinase from Escherichia coli. J. Biol. Chem., 269, 27051-27058.
47.Xu, X-X., Rock, C.O., Qiu, Z-H., Leslie, C.C., and Jackowski, S. (1994) Regulation of cytosolic phospholipase A2 phosphorylation and eicosanoid production by colony-stimulating factor 1. J. Biol. Chem., 269, 31693-1700.
48. Boggs, K.P., Rock, C.O., and Jackowski, S. (1995) Lysophosphatidylcholine and 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine inhibit the CDP-choline pathway of phosphatidyl-choline synthesis at the CTP:phosphocholine cytidylyltransferase step. J. Biol. Chem., 270, 7757-7764.
49.Boggs, K.P., Rock, C.O., and Jackowski, S. (1995) Lysophosphatidylcholine attenuates the cytotoxic effects of the antineoplastic phospholipid 1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine. J. Biol. Chem., 270, 11612-11618.
50.Vairo, G., Vadiveloo, P.K., Royston, A.K., Rockman, S.P., Rock, C.O., Jackowski, S., and Hamilton, J.A. (1995) Deregulated c-myc expression overrides IFNy-induced macrophage growth arrest. Oncogene, 10, 1969-1976.
51.Xu, X-X., Yang, W., Jackowski, S., and Rock, C.O. (1995) Cloning of a novel phosphoprotein regulated by colony-stimulating factor 1 shares a domain with the Drosophila disabled protein.
J. Biol. Chem., 270, 14184-14191.
52.Yang, W. and Jackowski, S. (1995) Lipid activation of CTP:phosphocholine cytidylyl-transferase is regulated by the phosphorylated carboxy terminal domain. J. Biol. Chem., 270, 16503-16506.

BOOK CHAPTERS:
9. Jackowski, S., Hsu, L., and Rock, C.O. (1992) 2-Acylglycerophosphoethanolamine acyltrans-ferase/acyl-acyl carrier protein synthetase from E. coli. Meth. Enzymol., 298, 111-117.
10. Magnuson, K., Jackowski, S., Rock, C.O., and Cronan, J.E., Jr. (1993) Regulation of fatty acid biosynthesis in Escherichia coli. Microbiol. Rev., 57, 552-542.
11. Rock, C.O. and Jackowski, S. (1995) Incorporation and turnover of fatty acids in Escherichia coli membrane phospholipids. In R.W. Gross (Ed.), Advances in molecular and cell biology - lipobiology. Greenwich, Connecticut: JAI Press, Inc., in press.
12. Jackowski, S. (1995) Biosynthesis of pantothenic acid and coenzyme A. In F.C. Neidhardt, R. Curtiss, C.A. Gross, J.L. Ingraham, E.C.C. Lin, K.B. Low, B. Magasanik, W. Reznikoff, M. Riley, M. Schaechter, and H.E. Umbarger (Eds.), Escherichia coli and Salmonella typhimurium: Cellular and molecular biology, Second edition. Washington, D.C.: American Society of Microbiology, in press.
13.Rock, C.O., Jackowski, S., and Cronan, J.E., Jr. (1996) Lipid metabolism in prokaryotes. In D.E. Vance and J. Vance (Eds.), The biochemistry of Lipids, Lipoproteins and membranes. Netherlands: Elsevier, in press.