H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway

Apolloni, A., Prior, I. A., Lindsay, M., Parton, R. G. and Hancock, J. F. (2000) H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway. Molecular & Cellular Biology, 20 7: 2475-2487. doi:10.1128/MCB.20.7.2475-2487.2000

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Author Apolloni, A.
Prior, I. A.
Lindsay, M.
Parton, R. G.
Hancock, J. F.
Title H-ras but not K-ras traffics to the plasma membrane through the exocytic pathway
Journal name Molecular & Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2000
Sub-type Article (original research)
DOI 10.1128/MCB.20.7.2475-2487.2000
Open Access Status File (Publisher version)
Volume 20
Issue 7
Start page 2475
End page 2487
Total pages 13
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2000
Language eng
Abstract Ras proteins must be localized to the inner surface of the plasma membrane to be biologically active. The motifs that effect Ras plasma membrane targeting consist of a C-terminal CAAX motif plus a second signal comprising palmitoylation of adjacent cysteine residues or the presence of a polybasic domain. In this study, we examined how Ras proteins access the cell surface after processing of the CAAX motif is completed in the endoplasmic reticulum (ER). We show that palmitoylated CAAX proteins, in addition to being localized at the plasma membrane, are found throughout the exocytic pathway and accumulate in the Golgi region when cells are incubated at 15 degrees C. In contrast, polybasic CAAX proteins are found only at the cell surface and not in the exocytic pathway. CAAX proteins which lack a second signal for plasma membrane targeting accumulate in the ER and Golgi. Brefeldin A (BFA) significantly inhibits the plasma membrane accumulation of newly synthesized, palmitoylated CAAX proteins without inhibiting their palmitoylation. BFA has no effect on the trafficking of polybasic CAAX proteins. We conclude that H-ras and K-ras traffic to the cell surface through different routes and that the polybasic domain is a sorting signal diverting K-Ras out of the classical exocytic pathway proximal to the Golgi. Farnesylated Ras proteins that lack a polybasic domain reach the Golgi but require palmitoylation in order to traffic further to the cell surface. These data also indicate that a Ras palmitoyltransferase is present in an early compartment of the exocytic pathway.
Keyword Biochemistry & Molecular Biology
Cell Biology
Regulatory Protein Gdi
N-ras
Saccharomyces-cerevisiae
Polybasic Domain
Terminal Proteolysis
Signaling Pathway
Molecular-cloning
A-factor
In-vivo
P21ras
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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Created: Tue, 10 Jun 2008, 10:33:00 EST