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Nat Cell Biol. 2001 Apr;3(4):368-75.

GTP-dependent segregation of H-ras from lipid rafts is required for biological activity.

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1
Laboratory of Experimental Oncology, Department of Pathology, University of Queensland Medical School, Herston Road, Queensland 4006, Australia.

Abstract

Different sites of plasma membrane attachment may underlie functional differences between isoforms of Ras. Here we show that palmitoylation and farnesylation targets H-ras to lipid rafts and caveolae, but that the interaction of H-ras with these membrane subdomains is dynamic. GTP-loading redistributes H-ras from rafts into bulk plasma membrane by a mechanism that requires the adjacent hypervariable region of H-ras. Release of H-ras-GTP from rafts is necessary for efficient activation of Raf. By contrast, K-ras is located outside rafts irrespective of bound nucleotide. Our studies identify a novel protein determinant that is required for H-ras function, and show that the GTP/GDP state of H-ras determines its lateral segregation on the plasma membrane.

Comment in

PMID:
11283610
DOI:
10.1038/35070050
[Indexed for MEDLINE]

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