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Originally published in Science Express on 10 February 2005
Science 18 March 2005:
Vol. 307. no. 5716, pp. 1746 - 1752
DOI: 10.1126/science.1105654
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Research Articles

An Acylation Cycle Regulates Localization and Activity of Palmitoylated Ras Isoforms

Oliver Rocks,1,3 Anna Peyker,3 Martin Kahms,1 Peter J. Verveer,3 Carolin Koerner,1 Maria Lumbierres,2 Jürgen Kuhlmann,1 Herbert Waldmann,2 Alfred Wittinghofer,1* Philippe I. H. Bastiaens3*

We show that the specific subcellular distribution of H- and Nras guanosine triphosphate–binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus. Depalmitoylation redistributes farnesylated Ras in all membranes, followed by repalmitoylation and trapping of Ras at the Golgi, from where it is redirected to the PM via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalization. The de/reacylation cycle also initiates Ras activation at the Golgi by transport of PM-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors.

1 Department of Structural Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.
2 Department of Chemical Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.
3 European Molecular Biology Laboratory, Meyerhofstraße 1, 69117 Heidelberg, Germany.

* To whom correspondence should be addressed. E-mail: alfred.wittinghofer{at}mpi-dortmund.mpg.de (A.W.) and bastiaen{at}embl.de (P.I.H.B.)

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