Three separable domains regulate GTP-dependent association of H-ras with the plasma membrane

Rotblat, B., Prior, I. A., Muncke, C., Parton, R. G., Kloog, Y., Henis, Y. I. and Hancock, J. F. (2004) Three separable domains regulate GTP-dependent association of H-ras with the plasma membrane. Molecular And Cellular Biology, 24 15: 6799-6810. doi:10.1128/MCB.24.15.6799-6810.2004

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Author Rotblat, B.
Prior, I. A.
Muncke, C.
Parton, R. G.
Kloog, Y.
Henis, Y. I.
Hancock, J. F.
Title Three separable domains regulate GTP-dependent association of H-ras with the plasma membrane
Journal name Molecular And Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
1098-5549
Publication date 2004
Sub-type Article (original research)
DOI 10.1128/MCB.24.15.6799-6810.2004
Open Access Status File (Publisher version)
Volume 24
Issue 15
Start page 6799
End page 6810
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2004
Language eng
Abstract The microlocalization of Ras proteins to different microdomains of the plasma membrane is critical for signaling specificity. Here we examine the complex membrane interactions of H-ras with a combination of FRAP on live cells to measure membrane affinity and electron microscopy of intact plasma membrane sheets to spatially map microdomains. We show that three separable forces operate on H-ras at the plasma membrane. The lipid anchor, comprising a processed CAAX motif and two palmitic acid residues, generates one attractive force that provides a high-affinity interaction with lipid rafts. The adjacent hypervariable linker domain provides a second attractive force but for nonraft plasma membrane microdomains. Operating against the attractive interaction of the lipid anchor for lipid rafts is a repulsive force generated by the N-terminal catalytic domain that increases when H-ras is GTP loaded. These observations lead directly to a novel mechanism that explains how H-ras lateral segregation is regulated by activation state: GTP loading decreases H-ras affinity for lipid rafts and allows the hypervariable linker domain to target to nonraft microdomains, the primary site of H-ras signaling.
Keyword Biochemistry & Molecular Biology
Cell Biology
Gpi-anchored Proteins
Lipid Rafts
Cell-surface
Lateral Mobility
Live Cells
Microdomains
Family
Signal
Q-Index Code C1

 
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Created: Wed, 15 Aug 2007, 04:46:51 EST