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Phospholipase Cγ activates Ras on the Golgi apparatus by means of RasGRP1

Author

Listed:
  • Trever G. Bivona

    (New York University School of Medicine)

  • Ignacio Pérez de Castro

    (New York University School of Medicine)

  • Ian M. Ahearn

    (New York University School of Medicine)

  • Theresa M. Grana

    (University of North Carolina at Chapel Hill School of Medicine)

  • Vi K. Chiu

    (New York University School of Medicine)

  • Peter J. Lockyer

    (The Babraham Institute)

  • Peter J. Cullen

    (University of Bristol School of Medical Sciences)

  • Angel Pellicer

    (New York University School of Medicine)

  • Adrienne D. Cox

    (University of North Carolina at Chapel Hill School of Medicine)

  • Mark R. Philips

    (New York University School of Medicine)

Abstract

Ras proteins regulate cellular growth and differentiation, and are mutated in 30% of cancers. We have shown recently that Ras is activated on and transmits signals from the Golgi apparatus as well as the plasma membrane1,2 but the mechanism of compartmentalized signalling was not determined. Here we show that, in response to Src-dependent activation of phospholipase Cγ1, the Ras guanine nucleotide exchange factor RasGRP1 translocated to the Golgi where it activated Ras. Whereas Ca2+ positively regulated Ras on the Golgi apparatus through RasGRP1, the same second messenger negatively regulated Ras on the plasma membrane by means of the Ras GTPase-activating protein CAPRI3. Ras activation after T-cell receptor stimulation in Jurkat cells, rich in RasGRP1, was limited to the Golgi apparatus through the action of CAPRI, demonstrating unambiguously a physiological role for Ras on Golgi. Activation of Ras on Golgi also induced differentiation of PC12 cells, transformed fibroblasts and mediated radioresistance. Thus, activation of Ras on Golgi has important biological consequences and proceeds through a pathway distinct from the one that activates Ras on the plasma membrane.

Suggested Citation

  • Trever G. Bivona & Ignacio Pérez de Castro & Ian M. Ahearn & Theresa M. Grana & Vi K. Chiu & Peter J. Lockyer & Peter J. Cullen & Angel Pellicer & Adrienne D. Cox & Mark R. Philips, 2003. "Phospholipase Cγ activates Ras on the Golgi apparatus by means of RasGRP1," Nature, Nature, vol. 424(6949), pages 694-698, August.
    • Handle: RePEc:nat:nature:v:424:y:2003:i:6949:d:10.1038_nature01806
    DOI: 10.1038/nature01806
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