QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 22 January 2008
doi: 10.1242/jcs.020107

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.020107v1 121/4/421    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laude, A. J. Articles by Prior, I. A. Search for Related Content PubMed PubMed Citation Articles by Laude, A. J. Articles by Prior, I. A. Social Bookmarking                         What's this?

Palmitoylation and localisation of RAS isoforms are modulated by the hypervariable linker domain

Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, UK

^* Author for correspondence (e-mail: iprior{at}liverpool.ac.uk)

Accepted 13 November 2007

RAS isoforms have been proposed to exhibit differing biological outputs due to differences in their relative occupancy of cellular organelles and signalling microdomains. The membrane binding and targeting motifs of RAS are encoded by the C-terminal hypervariable region (HVR), and the precise localisation depends upon interactions between the HVR and the host membrane. Classic studies revealed that all RAS proteins rely on farnesylation and either palmitoylation or a polybasic stretch for stable binding to membranes. We now show that, for N-RAS and Ki-RAS4A, mono-palmitoylation and farnesylation are not sufficient for specifying stable cell-surface localisation. A third motif that is present within the linker domain of all palmitoylated RAS HVRs is necessary for stabilising localisation to the plasma membrane. This motif comprises acidic residues that stabilise palmitoylation and basic amino acids that are likely to interact electrostatically with acidic phospholipids enriched at the cell surface. Importantly, altered localisation is achieved without changes in palmitoylation status. Our data provide a mechanism for distinct HVR membrane interactions controlling subcellular distribution. In the context of the full-length RAS proteins, this is likely to be of crucial importance for controlling signalling output and engagement with different pools of effectors.

Key words: RAS, Isoforms, Palmitoylation, Trafficking, Compartmentalisation

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Ras isoforms: the missing linker

JCS 2008 121: 401. [Full Text]  

This article has been cited by other articles:

				K. Inder, A. Harding, S. J. Plowman, M. R. Philips, R. G. Parton, and J. F. Hancock Activation of the MAPK Module from Different Spatial Locations Generates Distinct System Outputs Mol. Biol. Cell, November 1, 2008; 19(11): 4776 - 4784. [Abstract] [Full Text] [PDF]

				S. Eisenberg, K. Giehl, Y. I. Henis, and M. Ehrlich Differential Interference of Chlorpromazine with the Membrane Interactions of Oncogenic K-Ras and Its Effects on Cell Growth J. Biol. Chem., October 3, 2008; 283(40): 27279 - 27288. [Abstract] [Full Text] [PDF]