A novel small molecule regulator of guanine nucleotide exchange activity of ARF and golgi membrane trafficking Export

@article{citeulike:4139924, abstract = {An image-based phenotypic screen was developed to identify small molecule regulators of intracellular traffic. Using this screen we found that AG1478, a previous known inhibitor of epidermal growth factor receptor (EGFR), had an EGFR independent activity in inducing the disassembly of the Golgi in human cells. Similar to Brefeldin A (BFA), a known disrupter of the Golgi, AG1478 inhibits the activity of small GTPase ARF. Unlike BFA, AG1478 exhibits low cytotoxicity and selectively targets the cis-Golgi without affecting endosomal compartment. We show that AG1478 inhibits GBF1, a large nucleotide exchange factor for ARF, in a Sec7 domain dependent manner and mimics the phenotype of a GBF1 mutant that has an inactive mutation. The treatment with AG1478 leads to the recruitment of GBF1 to the VTCs adjacent to the ERES, a step only transiently observed previously in the presence of BFA. We propose that the treatment with AG1478 delineates a membrane trafficking intermediate step that depends upon the Sec7 domain. 10.1074/jbc.M806592200}, author = {Pan, Heling and Yu, Jia and Zhang, Lihong and Carpenter, Anne and Zhu, Hong and Li, Li and Ma, Dawei and Yuan, Junying}, citeulike-article-id = {4139924}, citeulike-linkout-0 = {http://dx.doi.org/10.1074/jbc.M806592200}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18799457}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18799457}, day = {17}, doi = {10.1074/jbc.M806592200}, journal = {J. Biol. Chem.}, keywords = {copi, gbf1, gef, golgi, in\_vivo, molecule, traffic}, month = {September}, pages = {M806592200+}, posted-at = {2009-03-31 12:50:45}, priority = {2}, title = {A novel small molecule regulator of guanine nucleotide exchange activity of ARF and golgi membrane trafficking}, url = {http://dx.doi.org/10.1074/jbc.M806592200}, year = {2008} }

TY - JOUR ID - citeulike:4139924 L3 - citeulike-article-id:4139924 N2 - An image-based phenotypic screen was developed to identify small molecule regulators of intracellular traffic. Using this screen we found that AG1478, a previous known inhibitor of epidermal growth factor receptor (EGFR), had an EGFR independent activity in inducing the disassembly of the Golgi in human cells. Similar to Brefeldin A (BFA), a known disrupter of the Golgi, AG1478 inhibits the activity of small GTPase ARF. Unlike BFA, AG1478 exhibits low cytotoxicity and selectively targets the cis-Golgi without affecting endosomal compartment. We show that AG1478 inhibits GBF1, a large nucleotide exchange factor for ARF, in a Sec7 domain dependent manner and mimics the phenotype of a GBF1 mutant that has an inactive mutation. The treatment with AG1478 leads to the recruitment of GBF1 to the VTCs adjacent to the ERES, a step only transiently observed previously in the presence of BFA. We propose that the treatment with AG1478 delineates a membrane trafficking intermediate step that depends upon the Sec7 domain. 10.1074/jbc.M806592200 JF - J. Biol. Chem. TI - A novel small molecule regulator of guanine nucleotide exchange activity of ARF and golgi membrane trafficking SP - M806592200 KW - copi KW - gbf1 KW - gef KW - golgi KW - in_vivo KW - molecule KW - traffic AU - Pan, Heling AU - Yu, Jia AU - Zhang, Lihong AU - Carpenter, Anne AU - Zhu, Hong AU - Li, Li AU - Ma, Dawei AU - Yuan, Junying PY - 2008/09/17/ UR - http://dx.doi.org/10.1074/jbc.M806592200 ER -