Mechanisms of Ras membrane organization and signalling: Ras on a rocker. Export

@article{citeulike:4019877, abstract = {Understanding the signalling function of Ras GTPases has been the focus of much research for over 20 years. Both the catalytic domain and the membrane anchoring C terminal hypervariable region (HVR) of Ras are necessary for its cellular function. However, while the highly conserved catalytic domain has been characterized in atomic detail, the structure of the full-length membrane-bound Ras has remained elusive. Lack of structural knowledge on the full-length protein limited our understanding of Ras signalling. For example, structures of the Ras catalytic domain solved in complex with effectors do not provide a basis for the functional specificity of different Ras isoforms. Recent molecular dynamics simulations in combination with biophysical and cell biological experiments have shown that the HVR and parts of the G domain cofunction with the lipid tails to anchor H-ras to the plasma membrane. In the GTP-bound state, H-ras adopts an orientation that allows read out by Ras effectors and translation into corresponding MAPK signalling. Here we discuss details of an analysis that suggests a novel balance model for Ras functioning. The balance model rationalizes Ras membrane orientation and may help explain isoform specific interactions of Ras with its effectors and modulators.}, author = {Abankwa, D. and Gorfe, A. A. and Hancock, J. F.}, citeulike-article-id = {4019877}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/18758236}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=18758236}, day = {1}, issn = {1551-4005}, journal = {Cell cycle (Georgetown, Tex.)}, keywords = {ras}, month = {September}, number = {17}, pages = {2667--2673}, posted-at = {2009-02-07 02:18:11}, priority = {2}, title = {Mechanisms of Ras membrane organization and signalling: Ras on a rocker.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18758236}, volume = {7}, year = {2008} }

TY - JOUR ID - citeulike:4019877 L3 - citeulike-article-id:4019877 N2 - Understanding the signalling function of Ras GTPases has been the focus of much research for over 20 years. Both the catalytic domain and the membrane anchoring C terminal hypervariable region (HVR) of Ras are necessary for its cellular function. However, while the highly conserved catalytic domain has been characterized in atomic detail, the structure of the full-length membrane-bound Ras has remained elusive. Lack of structural knowledge on the full-length protein limited our understanding of Ras signalling. For example, structures of the Ras catalytic domain solved in complex with effectors do not provide a basis for the functional specificity of different Ras isoforms. Recent molecular dynamics simulations in combination with biophysical and cell biological experiments have shown that the HVR and parts of the G domain cofunction with the lipid tails to anchor H-ras to the plasma membrane. In the GTP-bound state, H-ras adopts an orientation that allows read out by Ras effectors and translation into corresponding MAPK signalling. Here we discuss details of an analysis that suggests a novel balance model for Ras functioning. The balance model rationalizes Ras membrane orientation and may help explain isoform specific interactions of Ras with its effectors and modulators. IS - 17 JF - Cell cycle (Georgetown, Tex.) SN - 1551-4005 EP - 2673 TI - Mechanisms of Ras membrane organization and signalling: Ras on a rocker. VL - 7 SP - 2667 KW - ras AU - Abankwa, D AU - Gorfe, AA AU - Hancock, JF PY - 2008/09/01/ UR - http://view.ncbi.nlm.nih.gov/pubmed/18758236 ER -