Abstract
AN early response to the tyrosine kinase activity of v-Src is an increase in phospholipase D (PLD) activity1, which leads to the generation of biologically active lipid second messengers, including phosphatidic acid, lysophosphatidic acid and diacylglycerol2. We have recently demonstrated that v-Src-induced PLD activity is mediated by Ras3, although Ras involvement was indirect, requiring a cytosolic factor for PLD activation3. Ras interacts with4–6 and activates Ral–GDS13, the exchange factor responsible for the activation of Ral GTPases. Here we report that this newly identified Ras/Ral signalling pathway mediates PLD activation by v-Src. PLD activity could be precipitated from v-Src-transformed cell lysates with immobilized RalA protein and with an anti-Ral antibody. A mutation to the region of RalA analogous to the 'effector domain' of Ras did not reduce the ability of RalA to complex with PLD, although deletion of a Ral-specific amino-terminal region did. Overexpression of RalA potentiated PLD activation by v-Src, and expression of dominant negative RalA mutants inhibited both v-Src- and v-Ras-induced PLD activity. Thus RalA is involved in the tyrosine kinase activation of PLD through its unique N terminus, and that PLD is a downstream target of a Ras/Ral GTPase cascade.
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Jiang, H., Luo, JQ., Urano, T. et al. Involvement of Ral GTPase in v-Src-induced phospholipase D activation. Nature 378, 409–412 (1995). https://doi.org/10.1038/378409a0
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DOI: https://doi.org/10.1038/378409a0
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