CHARLES O. ROCK
PROFESSOR

EDUCATION:
B.S. 1971, Colorado State University, Ft. Collins, Colorado
Ph.D. 1976, University of Tennessee at Oak Ridge, Tennessee

RESEARCH INTERESTS: The focus of my research relates to signal transduction and the regulation of phospholipid metabolism. Current work relates to the characterization of phosphatidylcholine-specific phospholipase C and its regulation by growth factors. Our results indicate that the activation of phosphatidylcholine phospholipase C is a significant step in the stimulation of cell growth by the macrophage growth factor CSF-1. Many of the early mitogenic effects of CSF-1 are mimicked by the addition of recombinant phospholipase C to the medium. We have recently cloned the cDNA for a novel protein in the CSF-1 signal transduction pathway and the molecular and biochemical characterization of this protein is an important future goal. Also, the laboratory is actively investigating the regulation of fatty acid and phospholipid synthesis in E. coli. Key regulatory enzymes are being cloned and mutagenized to verify their role in pathway control. Techniques used in both projects include gene expression in bacterial and mammalian systems, site-directed mutagenesis, cloning and sequence analysis and the physical and kinetic characterization of purified proteins.

CURRENT RESEARCH SUPPORT:
NIGMS 5 RO1 GM34496 on "Regulation of Fatty Acid Biosynthesis" December 1, 1992 - November 31, 1996; $849,444.

GRADUATE STUDENTS:
At the University of Tennessee, Memphis: 1982-1986, David Vallari, Ph.D.

PUBLICATIONS: (Only selected publications appearing since 1989 are listed.)
61. Cooper, C.L., Hsu, L., Jackowski, S. and Rock, C.O. (1989) 2-Acylglycerolphosphoethanolamine acyltransferase/acyl-acyl carrier protein synthetase is a membrane-associated acyl carrier protein binding protein. J. Biol. Chem., 264, 7384-7389.
62. Jackowski, S., Murphy, C.M., Cronan, J.E., Jr. and Rock, C.O. (1989) Acetoacetyl-acyl carrier protein synthase: A target for the antibiotic thiolactomycin.
J. Biol. Chem., 264, 7624-7629.
63. Jackowski, S., Rettenmier, C.W., and Rock, C.O. (1990) Prostaglandin E2 inhibition of growth in a colony-stimulating factor 1-dependent macrophage cell line.
J. Biol. Chem., 265, 6611-6616.
64. Shurtleff, S.A., Downing, J.R., Rock, C.O., Hawkins, S.A., Roussel, M.F., and Sherr, C.J. (1990) Structural features of the colony-stimulating factor 1 receptor that affect its association with phosphatidylinositol 3-kinase. EMBO Journal, 9, 2415-2421.
65. Hsu, L., Jackowski, S., and Rock, C.O. (1991) Isolation and characterization of Escherichia coli K-12 mutants lacking both 2-acylglycerophosphoethanolamine acyltransferase and acyl-acyl carrier protein synthetase activity. J. Biol. Chem., 266, 13783-13788.
66. Tessner, T., Rock, C.O., Kalmar, G.M., Cornell, R.B., and Jackowski, S. (1991) Colony- stimulating factor 1 regulates CTP:phosphocholine cytidylyltransferase mRNA levels.
J. Biol. Chem., 266, 16261-16264.
67. Tsay, J-T, Rock, C.O., and Jackowski, S. (1992) Overproduction of ß-ketoacyl-ACP synthase I imparts thiolactomycin resistance to Escherichia coli K-12. J. Bacteriol., 174, 508-513.
68. 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. Molec. Cell Biol., 12, 2351-2358.
69. Tsay, J-T, Oh, W., Larson, T.J., Jackowski, S., and Rock, C.O. (1992) Isolation and characterization of the ß-ketoacyl-acyl carrier protein synthase III gene (fabH) from Escherichia coli K-12. J. Biol. Chem., 267, 6807-6814.
70. Li, S., Rock, C., and Cronan, Jr., J.E. (1992) The dedB/usg open reading frame of Escherichia coli encodes a subunit of acetyl-CoA carboxylase. J. Bacteriol., 174, 5755-5757.
71. 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.
72. 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.
73. 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.
74. 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.
75. 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.
76.Cronan, Jr., J.E. and Rock, C.O. (1994) The presence of linoleic acid in Escherichia coli cannot be confirmed. J. Bacteriol., 176, 3069-3071.
77.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., 266, 26584-26590.
78.Xu, X-X., Rock, C.O., Qui, 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, 31693-31700.
79. 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.
80.Vairo, G., Vadiveloo, P.K., Royston, A.K., Rockman, S.P., Rock, C.O., Jackowski, S., and Hamilton, J.A. (1995) Deregulation c-myc expression overrides IFNy-induced macrophage growth arrest. Oncogene, 10, 1969-1976.
81.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.
82.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 gene product. J. Biol. Chem., 270, 14184-14191.
83.Heath, R.J. and Rock, C.O. (1995) Regulation of malonyl-CoA metabolism by acyl-acyl carrier protein and B-ketoacyl-acyl carrier protein synthases in Escherichia coli. J. Biol. Chem., 270, 15531-15538.
84.Heath, R.J. and Rock, C.O. (1995) Enoyl-acyl carrier protein reductase (fabl) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli.
J. Biol. Chem., in press.