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J. Biol. Chem., Vol. 279, Issue 13, 12081-12087, March 26, 2004

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Regulation of Phospholipid Synthesis in the Yeast cki1 eki1 Mutant Defective in the Kennedy Pathway

THE CHO1-ENCODED PHOSPHATIDYLSERINE SYNTHASE IS REGULATED BY mRNA STABILITY^*

Hyeon-Son Choi, Avula Sreenivas, Gil-Soo Han, and George M. Carman

From the Department of Food Science, Rutgers University, New Brunswick, New Jersey 08901

In the yeast Saccharomyces cerevisiae, the most abundant phospholipid phosphatidylcholine is synthesized by the complementary CDP-diacylglycerol and Kennedy pathways. Using a cki1 eki1 mutant defective in choline kinase and ethanolamine kinase, we examined the consequences of a block in the Kennedy pathway on the regulation of phosphatidylcholine synthesis by the CDP-diacylglycerol pathway. The cki1 eki1 mutant exhibited increases in the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine via the CDP-diacylglycerol pathway. The increase in phospholipid synthesis correlated with increased activity levels of the CDP-diacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. However, other enzyme activities, including phosphatidylinositol synthase and phosphatidate phosphatase, were not affected in the cki1 eki1 mutant. For phosphatidylserine synthase, the enzyme catalyzing the committed step in the pathway, activity was regulated by increases in the levels of mRNA and protein. Decay analysis of CHO1 mRNA indicated that a dramatic increase in transcript stability was a major component responsible for the elevated level of phosphatidylserine synthase. These results revealed a novel mechanism that controls phospholipid synthesis in yeast.

Received for publication, January 12, 2004 , and in revised form, January 21, 2004.

^* This work was supported in part by the United States Public Health Service, National Institutes of Health Grant GM-50679. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence and reprint requests should be addressed. Dept. of Food Science, Rutgers University, 65 Dudley Rd., New Brunswick, NJ 08901. Tel.: 732-932-9611 (ext. 217); E-mail: carman{at}aesop.rutgers.edu.

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This article has been cited by other articles:

				H.-S. Choi and G. M. Carman Respiratory Deficiency Mediates the Regulation of CHO1-encoded Phosphatidylserine Synthase by mRNA Stability in Saccharomyces cerevisiae J. Biol. Chem., October 26, 2007; 282(43): 31217 - 31227. [Abstract] [Full Text] [PDF]

				W. M. Iwanyshyn, G.-S. Han, and G. M. Carman Regulation of Phospholipid Synthesis in Saccharomyces cerevisiae by Zinc J. Biol. Chem., May 21, 2004; 279(21): 21976 - 21983. [Abstract] [Full Text] [PDF]