We recently reported that DAG (diacylglycerol) generated during sphingomyelin synthesis plays an important role in protein kinase C activation and cell proliferation in Madin–Darby canine kidney cells [Cerbon and Lopez-Sanchez (2003) Biochem. J. 373, 917–924]. In yeast cells, IPC (inositol phosphoceramide) synthase catalyses the transfer of phosphoinositol from phosphatidylinositol to ceramide to form IPC and generates DAG. In the present study, we found that, during the G1 to S transition after N2-starvation, there was a significant increase in the synthesis of IPC accompanied by a progressive increase (up to 6-fold) in the level of DAG. The increased DAG levels coincided with decrements in ceramide and sphingoid base levels, conditions that are adequate for the activation of putative protein kinase C required for the G1 to S transition and proliferation of yeast cells. To separate the role of DAG generated during IPC synthesis from that originating from other sources, we utilized β-chloroalanine and myriocin, inhibitors of serine:palmitoyl-CoA transferase, the first committed step in sphingolipid synthesis, to avoid accumulation of sphingolipid intermediates. When the synthesis of sphingolipids was inhibited, DAG accumulation was significantly decreased and the G1 to S transition was blocked; such blockage was avoided by metabolic complementation with phytosphingosine. The DAG/ceramide ratio was 0.27 and it changed to 2.0 during growth re-initiation, suggesting that the synthesis of phosphosphingolipids could act to switch growth arrest (increased ceramide) to a mitogenic signal (increased DAG), and that this signalling process is preserved in yeast and mammalian cells.
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May 2005
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Research Article|
May 10 2005
Inositol phosphoceramide synthase is a regulator of intracellular levels of diacylglycerol and ceramide during the G1 to S transition in Saccharomyces cerevisiae
Jorge CERBÓN;
Jorge CERBÓN
1
1Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del IPN, 07000 México, D.F., México
1To whom correspondence should be addressed (email [email protected]).
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Alejandro FALCON;
Alejandro FALCON
1Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del IPN, 07000 México, D.F., México
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Carlos HERNÁNDEZ-LUNA;
Carlos HERNÁNDEZ-LUNA
1Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del IPN, 07000 México, D.F., México
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David SEGURA-COBOS
David SEGURA-COBOS
1Department of Biochemistry, Centro de Investigación y de Estudios Avanzados del IPN, 07000 México, D.F., México
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Publisher: Portland Press Ltd
Received:
March 23 2004
Revision Received:
November 16 2004
Accepted:
November 24 2004
Accepted Manuscript online:
November 24 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 388 (1): 169–176.
Article history
Received:
March 23 2004
Revision Received:
November 16 2004
Accepted:
November 24 2004
Accepted Manuscript online:
November 24 2004
Citation
Jorge CERBÓN, Alejandro FALCON, Carlos HERNÁNDEZ-LUNA, David SEGURA-COBOS; Inositol phosphoceramide synthase is a regulator of intracellular levels of diacylglycerol and ceramide during the G1 to S transition in Saccharomyces cerevisiae. Biochem J 15 May 2005; 388 (1): 169–176. doi: https://doi.org/10.1042/BJ20040475
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