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http://purl.uniprot.org/citations/11094076http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/11094076http://www.w3.org/2000/01/rdf-schema#comment"Sphingosine-1-phosphate (S1P) is a bioactive lysophospholipid that induces a variety of biological responses in diverse cell types. Many, if not all, of these responses are mediated by members of the EDG (endothelial differentiation gene) family G protein-coupled receptors EDG1, EDG3, and EDG5 (AGR16). Among prominent activities of S1P is the regulation of cell motility; S1P stimulates or inhibits cell motility depending on cell types. In the present study, we provide evidence for EDG subtype-specific, contrasting regulation of cell motility and cellular Rac activity. In CHO cells expressing EDG1 or EDG3 (EDG1 cells or EDG3 cells, respectively) S1P as well as insulin-like growth factor I (IGF I) induced chemotaxis and membrane ruffling in phosphoinositide (PI) 3-kinase- and Rac-dependent manners. Both S1P and IGF I induced a biphasic increase in the amount of the GTP-bound active form of Rac. In CHO cells expressing EDG5 (EDG5 cells), IGF I similarly stimulated cell migration; however, in contrast to what was found for EDG1 and EDG3 cells, S1P did not stimulate migration but totally abolished IGF I-directed chemotaxis and membrane ruffling, in a manner dependent on a concentration gradient of S1P. In EDG5 cells, S1P stimulated PI 3-kinase activity as it did in EDG1 cells but inhibited the basal Rac activity and totally abolished IGF I-induced Rac activation, which involved stimulation of Rac-GTPase-activating protein activity rather than inhibition of Rac-guanine nucleotide exchange activity. S1P induced comparable increases in the amounts of GTP-RhoA in EDG3 and EDG5 cells. Neither S1P nor IGF I increased the amount of GTP-bound Cdc42. However, expression of N(17)-Cdc42, but not N(19)-RhoA, suppressed S1P- and IGF I-directed chemotaxis, suggesting a requirement for basal Cdc42 activity for chemotaxis. Taken together, the present results demonstrate that EDG5 is the first example of a hitherto-unrecognized type of receptors that negatively regulate Rac activity, thereby inhibiting cell migration and membrane ruffling."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.org/dc/terms/identifier"doi:10.1128/mcb.20.24.9247-9261.2000"xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/author"Okamoto H."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/author"Sugimoto N."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/author"Shigematsu H."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/author"Takuwa Y."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/author"Yokomizo T."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/author"Takuwa N."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/author"Sakurada S."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/date"2000"xsd:gYear
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/name"Mol Cell Biol"xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/pages"9247-9261"xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/title"Inhibitory regulation of Rac activation, membrane ruffling, and cell migration by the G protein-coupled sphingosine-1-phosphate receptor EDG5 but not EDG1 or EDG3."xsd:string
http://purl.uniprot.org/citations/11094076http://purl.uniprot.org/core/volume"20"xsd:string
http://purl.uniprot.org/citations/11094076http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/11094076
http://purl.uniprot.org/citations/11094076http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/11094076
http://purl.uniprot.org/uniprot/P48303#attribution-5B35DBB52037D29094330E639DEC2273http://purl.uniprot.org/core/sourcehttp://purl.uniprot.org/citations/11094076
http://purl.uniprot.org/uniprot/#_P48303-mappedCitation-11094076http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/11094076
http://purl.uniprot.org/uniprot/P48303http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/11094076