Letter | Published:

Involvement of Ral GTPase in v-Src-induced phospholipase D activation

Nature volume 378, pages 409412 (23 November 1995) | Download Citation

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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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Affiliations

  1. The Institute for Biomolecular Structure and Function, and Department of Biological Sciences, The Hunter College of The City University of New York, 695 Park Avenue, New York, New York 10021, USA

    • Hong Jiang
    • , Jing-Qing Luo
    • , Paul Frankel
    • , Zhimin Lu
    •  & David A. Foster
  2. The Institute for Biomolecular Structure and Function, and Department of Biological Sciences, The Hunter College of The City University of New York, 695 Park Avenue, New York, New York 10021, USA

    • Hong Jiang
    • , Jing-Qing Luo
    • , Paul Frankel
    • , Zhimin Lu
    •  & David A. Foster
  3. The Institute for Biomolecular Structure and Function, and Department of Biological Sciences, The Hunter College of The City University of New York, 695 Park Avenue, New York, New York 10021, USA

    • Hong Jiang
    • , Jing-Qing Luo
    • , Paul Frankel
    • , Zhimin Lu
    •  & David A. Foster
  4. Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA

    • Takeshi Urano
    •  & Larry A. Feig
  5. Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA

    • Takeshi Urano
    •  & Larry A. Feig

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https://doi.org/10.1038/378409a0

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