Abstract

Studies on the mechanisms and control of energy-transducing systems in normal and tumor cells will be continued. Three ATP-driven ion pumps from normal tissues will be analyzed: the H?+? pump of clathrin-coated vesicles from bovine brain, the Ca?2+? pump of sarcomplasmic reticulum of rabbit muscle, and the Na?+?K?+? ATPase from dog kidney. The proton pump has been solubilized and will be purified to homogeneity. A hydrophobic membrane fragment of the clathrin-coated vesicle was shown to be required for reconstitution. This will also be purified. The Ca?2+? pump will be reconstituted with synthetic and natural phospholipids and proteolipids, and conditions regulating the efficiency of pumping will be explored. Similar studies will be performed with the Na?+?K?+? ATPase. Glycolysis in tumor cells will be analyzed with respect to the ATPases required for the delivery of ADP and P?i?. We shall explore how oncogenes increase the rate of aerobic glycolysis. Growth factors such as TGFs known to stimulate glycolysis will be analyzed and their connections with oncogenes explored. A recent discovery showing that methionine at 10 mM inhibits glycolysis of transformed cells or untransformed cells that have been exposed to transforming factor beta will be further analyzed in great detail. (E)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA008964-22
Application #
3163337
Study Section
(SSS)
Project Start
1976-09-30
Project End
1990-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
22
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
Cornell University
Department
Type
Schools of Arts and Sciences
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850

  Publications

Adamikova, L; Resnick, R J; Tomaska, L (1996) Enrichment of yeast protein tyrosine kinase activity by substrate affinity chromatography. Yeast 12:833-8
Lin, P H; Shenoy, S; Galitski, T et al. (1995) Transformation of mouse cells by wild-type mouse c-Src. Oncogene 10:401-5
Resnick, R J; Tomaska, L (1994) Stimulation of yeast adenylyl cyclase activity by lysophospholipids and fatty acids. Implications for the regulation of Ras/effector function by lipids. J Biol Chem 269:32336-41
Chackalaparampil, I; Bagrodia, S; Shalloway, D (1994) Tyrosine dephosphorylation of pp60c-src is stimulated by a serine/threonine phosphatase inhibitor. Oncogene 9:1947-55
Brandt, R; Lee, G; Teplow, D B et al. (1994) Differential effect of phosphorylation and substrate modulation on tau's ability to promote microtubule growth and nucleation. J Biol Chem 269:11776-82
Tomaska, L; Resnick, R J (1993) Suppression of platelet-derived growth factor receptor tyrosine kinase activity by unsaturated fatty acids. J Biol Chem 268:5317-22
Tomaska, L; Resnick, R J (1993) Involvement of a phosphotyrosine protein phosphatase in the suppression of platelet-derived growth factor receptor autophosphorylation in ras-transformed cells. Biochem J 293 ( Pt 1):215-21
Racker, E (1992) Chaperones and matchmakers: inhibitors and stimulators of protein phosphorylation. Curr Top Cell Regul 33:127-43
Abdel-Ghany, M; Osusky, M; Igarashi, Y et al. (1992) Substrate-specific modulation of Src-mediated phosphorylation of Ras and caseins by sphingosines and other substrate modulators. Biochim Biophys Acta 1137:349-55
Mawal-Dewan, M; Sen, P C; Abdel-Ghany, M et al. (1992) Phosphorylation of tau protein by purified p34cdc28 and a related protein kinase from neurofilaments. J Biol Chem 267:19705-9

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