Ral and Rho-dependent activation of phospholipase D in v-Raf-transformed cells.

Citation data:

Biochemical and biophysical research communications, ISSN: 0006-291X, Vol: 255, Issue: 2, Page: 502-7

Publication Year:
1999
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Abstract Views 3
Captures 5
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Citations 44
Citation Indexes 44
PMID:
10049738
DOI:
10.1006/bbrc.1999.0234
Author(s):
Paul Frankel; Miguel Ramos; Judith Flom; Sergei Bychenok; Troy Joseph; Eugen Kerkhoff; Ulf R. Rapp; Larry A. Feig; David A. Foster
Publisher(s):
Elsevier BV
Tags:
Biochemistry, Genetics and Molecular Biology
article description
Phospholipase D (PLD) activity is commonly elevated in response to mitogenic signals. We reported previously that although the transformed phenotype induced by v-Src was dependent upon Raf-1, the PLD activity induced by v-Src was independent of Raf-1. This observation suggested to us that Raf would not likely be an activator of PLD. However, upon examination of PLD activity in v-Raf-transformed cells, surprisingly, we found that PLD activity is elevated to levels that were even higher than that observed in v-Src-transformed cells. To characterize the mechanism of v-Raf-induced PLD activity, we examined the dependence of v-Raf-induced PLD activity upon protein kinase C (PKC) the small GTPases Ral and Rho, which have all been implicated in the activation of PLD. The v-Raf-induced PLD activity was inhibited by dominant negative mutants for both Ral and Rho. The dependence upon Ral was particularly surprising since Ral is a downstream target of Ras, which is an upstream activator of Raf. Depleting cells of PKC by long term phorbol ester treatment actually increased PLD activity in v-Raf-transformed cells, indicating that v-Raf-induced PLD activity is not dependent on PKC. These data describe a novel mechanism for PLD activation by v-Raf that is independent of PKC, but dependent upon both Ral and Rho GTPases.