Hydrolysis of phosphatidylcholine couples Ras to activation of Raf protein kinase during mitogenic signal transduction.

TitleHydrolysis of phosphatidylcholine couples Ras to activation of Raf protein kinase during mitogenic signal transduction.
Publication TypeJournal Article
Year of Publication1993
AuthorsCai H, Erhardt P, Troppmair J, Diaz-Meco MT, Sithanandam G, Rapp UR, Moscat J, Cooper GM
JournalMol Cell Biol
Volume13
Issue12
Pagination7645-51
Date Published1993 Dec
ISSN0270-7306
Keywords3T3 Cells, Animals, Cell Division, Enzyme Activation, Genes, ras, Hydrolysis, Mice, Mutation, Phosphatidylcholines, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-raf, Signal Transduction, Transfection, Type C Phospholipases
Abstract

We have investigated the relationship between hydrolysis of phosphatidylcholine (PC) and activation of the Raf-1 protein kinase in Ras-mediated transduction of mitogenic signals. As previously reported, cotransfection of a PC-specific phospholipase C (PC-PLC) expression plasmid bypassed the block to cell proliferation resulting from expression of the dominant inhibitory mutant Ras N-17. In contrast, PC-PLC failed to bypass the inhibitory effect of dominant negative Raf mutants, suggesting that PC-PLC functions downstream of Ras but upstream of Raf. Consistent with this hypothesis, treatment of quiescent cells with exogenous PC-PLC induced Raf activation, even when normal Ras function was blocked by Ras N-17 expression. Further, activation of Raf in response to mitogenic growth factors was blocked by inhibition of endogenous PC-PLC. Taken together, these results indicate that hydrolysis of PC mediates Raf activation in response to mitogenic growth factors.

DOI10.1128/mcb.13.12.7645-7651.1993
Alternate JournalMol Cell Biol
PubMed ID8246981
PubMed Central IDPMC364836
Grant ListR01 CA18689 / CA / NCI NIH HHS / United States
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Jorge Moscat, Ph.D. Maria Diaz-Meco Conde, Ph.D.

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