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

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 and Mark R. Philips ()
Additional contact information
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

Nature, 2003, vol. 424, issue 6949, 694-698

Abstract: 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.

Date: 2003
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature01806 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:424:y:2003:i:6949:d:10.1038_nature01806

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01806

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().