An Arf1 GTPase mutant with different responses to GEF inhibitors. Export

@article{citeulike:3500543, abstract = {Guanine nucleotide exchange factors (GEFs) stimulate the activation of small GTP-binding proteins (GTPases). Establishing their specificity is a challenging issue, in which chemical genetics are rapidly gaining interest. We report a mutation in the Arf1 GTPase, K38A, which differentially alters its sensitivity to GEF inhibitors. The mutation renders Arf1 insensitive to LM11, a GEF inhibitor that we previously discovered by structure-based screening. In contrast, full inhibition by the natural compound Brefeldin A (BFA) is retained. We show that the mutation is otherwise silent towards the biochemical and cellular properties of Arf1, notably its binding to effectors as measured by a novel GEF-protection assay. This is thus the first GTPase mutant with different responses to two classes of inhibitors, and a novel tool to analyze Arf and ArfGEF specificity and functions in vitro and in cells.}, author = {Flisiak, S. and Zeeh, J. C. and Guibert, B. and Cherfils, J. and Zeghouf, M.}, citeulike-article-id = {3500543}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.bbrc.2008.09.107}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18834864}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18834864}, doi = {10.1016/j.bbrc.2008.09.107}, issn = {1090-2104}, journal = {Biochemical and biophysical research communications}, keywords = {arf1, curvature, gef, interactions, mutant, regulation}, month = {December}, number = {1}, pages = {156--160}, posted-at = {2008-11-10 08:14:45}, priority = {2}, title = {An Arf1 GTPase mutant with different responses to GEF inhibitors.}, url = {http://dx.doi.org/10.1016/j.bbrc.2008.09.107}, volume = {377}, year = {2008} }

TY - JOUR ID - citeulike:3500543 L3 - citeulike-article-id:3500543 N2 - Guanine nucleotide exchange factors (GEFs) stimulate the activation of small GTP-binding proteins (GTPases). Establishing their specificity is a challenging issue, in which chemical genetics are rapidly gaining interest. We report a mutation in the Arf1 GTPase, K38A, which differentially alters its sensitivity to GEF inhibitors. The mutation renders Arf1 insensitive to LM11, a GEF inhibitor that we previously discovered by structure-based screening. In contrast, full inhibition by the natural compound Brefeldin A (BFA) is retained. We show that the mutation is otherwise silent towards the biochemical and cellular properties of Arf1, notably its binding to effectors as measured by a novel GEF-protection assay. This is thus the first GTPase mutant with different responses to two classes of inhibitors, and a novel tool to analyze Arf and ArfGEF specificity and functions in vitro and in cells. IS - 1 JF - Biochemical and biophysical research communications SN - 1090-2104 EP - 160 TI - An Arf1 GTPase mutant with different responses to GEF inhibitors. VL - 377 SP - 156 KW - arf1 KW - curvature KW - gef KW - interactions KW - mutant KW - regulation AU - Flisiak, S AU - Zeeh, JC AU - Guibert, B AU - Cherfils, J AU - Zeghouf, M PY - 2008/12/05/ UR - http://dx.doi.org/10.1016/j.bbrc.2008.09.107 ER -