Molecular Biology of the Cell click for CBE Life Science Education Page

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

MBC in Press, published online ahead of print August 26, 2009
Mol. Biol. Cell 10.1091/mbc.E09-03-0247

A more recent version of this article appeared on October 15, 2009
This Article
Right arrow Full Text (PDF)
Right arrow Supplemental Materials
Right arrow All Versions of this Article:
E09-03-0247v1
20/20/4400    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Erlmann, P.
Right arrow Articles by Olayioye, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Erlmann, P.
Right arrow Articles by Olayioye, M. A.

Submitted on March 26, 2009
Revised on August 13, 2009
Accepted on August 18, 2009

DLC1 Activation Requires Lipid Interaction through a Polybasic Region Preceding the RhoGAP Domain

Patrik Erlmann,* Simone Schmid,* Florian A. Horenkamp,{dagger} Matthias Geyer,{dagger} Thomas G. Pomorski,{ddagger} and Monilola A. Olayioye*

*Institute of Cell Biology and Immunology, University of Stuttgart, 70569 Stuttgart, Germany; {dagger}Department of Physical Biochemistry, Max-Planck-Institute of Molecular Physiology, 44227 Dortmund, Germany; {ddagger}Department of Plant Biology and Biotechnology, University of Copenhagen, 1871 Frederiksberg C, Denmark

Monitoring Editor: David G. Drubin

Deleted in Liver Cancer 1 (DLC1) is a GTPase activating protein (GAP) with specificity for RhoA, RhoB and RhoC that is frequently deleted in various tumor types. By inactivating these small GTPases, DLC1 controls actin cytoskeletal remodeling and biological processes such as cell migration and proliferation. Here we provide evidence that DLC1 binds to phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2) through a previously unrecognized polybasic region (PBR) adjacent to its RhoGAP domain. Importantly, PI(4,5)P2-containing membranes are shown to stimulate DLC1 GAP activity in vitro. In living cells, a DLC1 mutant lacking an intact PBR inactivated Rho signaling less efficiently and was severely compromised in suppressing cell spreading, directed migration and proliferation. We therefore propose that PI(4,5)P2 is an important cofactor in DLC1 regulation in vivo and that the PBR is essential for the cellular functions of the protein.

Address correspondence to: Monilola A. Olayioye (monilola.olayioye{at}izi.uni-stuttgart.de)






Home Help [Feedback] [For Subscribers] [Archive] [Search] --
Copyright © 2009 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.