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  • Original Paper
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Regulation of choline kinase activity by Ras proteins involves Ral–GDS and PI3K

Oncogene volume 21, pages 937–946 (2002)Cite this article

Abstract

Ras proteins are molecular switches that control signaling pathways critical in the onset of a variety of human cancers. The signaling pathways activated by Ras proteins are those controlled by its direct effectors such as the serine-threonine protein kinase Raf-1, the exchange factor for other GTPases Ral–GDS, and the lipid kinase PI3K. As a consequence of Ras activation, a number of additional enzymes are affected, including several members of the serine-threonine intracellular proteins kinases as well as enzymes related to phospholipid metabolism regulation such as phospholipases A2 and D, and choline kinase. The precise mechanisms by which ras oncogenes impinge into these later molecules and their relevance to the onset of the carcinogenic process is still not fully understood. Here we have investigated the mechanism of regulation of choline kinase by Ras proteins and found no direct link between PLD and choline kinase activation. We provide evidence that Ras proteins regulate the activity of choline kinase through its direct effectors Ral–GDS and PI3K, while the Raf pathways seems to be not relevant in this process. The importance of Ras-dependent activation of choline kinase is discussed.

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Acknowledgements

We gratefully thank Drs J Downward, P Crespo, MA Frohman and S Yamashita for kindly providing us with the correspondent genes mentioned in the text. This work was supported by Grant 2FD1997-1569 from CICYT, Grant 99/0817 from FIS, Grant 08.1/0045.1/98 from Consejería de Educación of Comunidad de Madrid, and a special Grant from Roche Diagnostics GmbH, Pharma Research Penzberg (Alemania). A. Ramírez de Molina is a fellow from Fondo de Investigación Sanitaria (Instituto de Salud Carlos III), grant BEFI 99/9125 (Ref. CPC/CLC).

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  1. Instituto de Investigaciones Biomédicas, CSIC, Arturo Duperier 4, Madrid, 28029, Spain

    Ana Ramírez de Molina, Verónica Penalva, Luisa Lucas & Juan Carlos Lacal

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  1. Ana Ramírez de Molina
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  2. Verónica Penalva
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Correspondence to Juan Carlos Lacal.

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Ramírez de Molina, A., Penalva, V., Lucas, L. et al. Regulation of choline kinase activity by Ras proteins involves Ral–GDS and PI3K. Oncogene 21, 937–946 (2002). https://doi.org/10.1038/sj.onc.1205144

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