| http://purl.uniprot.org/citations/16714282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/16714282 | http://www.w3.org/2000/01/rdf-schema#comment | "The cycling of the small Rho family GTPase Cdc42 is required for insulin granule exocytosis, although the regulatory proteins involved in Cdc42 cycling in pancreatic beta-cells are unknown. Here we demonstrate that the caveolar protein caveolin-1 (Cav-1) is a Cdc42-binding protein in beta-cells. Cav-1 associated with Cdc42-VAMP2-bound granules present near the plasma membrane under basal conditions. However, stimulation with glucose induced the dissociation of Cav-1 from Cdc42-VAMP2 complexes, coordinate with the timing of Cdc42 activation. Analyses of the Cav-1 scaffolding domain revealed a motif conserved in guanine nucleotide dissociation inhibitors (GDIs), which suggested a novel role for Cav-1 as a Cdc42 GDI in beta-cells. The novel role was further supported by: 1) in vitro binding analyses that demonstrated a direct interaction between Cav-1 and Cdc42; 2) GST-Cdc42 interaction assays showing preferential Cav-1 binding to GDP-Cdc42 over that of GTP-Cdc42; 3) Cav-1 depletion studies resulting in an inappropriate 40% induction of activated Cdc42 in the absence of stimuli and also a 40% increase in basal insulin release from both MIN6 cells and islets. Expression of wild-type Cav-1 in Cav-1-depleted cells restored basal level secretion to normal, whereas expression of a scaffolding domain mutant of Cav-1 failed to normalize secretion. Taken together, these data suggest that Cav-1 functions as a Cdc42 GDI in beta-cells, maintaining Cdc42 in an inactive state and regulating basal secretion in the absence of stimuli. Through its interaction with the Cdc42-VAMP2-bound insulin granule complex, Cav-1 may contribute to the specific targeting of granules to "active sites" of exocytosis organized by caveolae."xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m603604200"xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://purl.uniprot.org/core/author | "Thurmond D.C."xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://purl.uniprot.org/core/author | "Nevins A.K."xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://purl.uniprot.org/core/date | "2006"xsd:gYear |
| http://purl.uniprot.org/citations/16714282 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://purl.uniprot.org/core/pages | "18961-18972"xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://purl.uniprot.org/core/title | "Caveolin-1 functions as a novel Cdc42 guanine nucleotide dissociation inhibitor in pancreatic beta-cells."xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://purl.uniprot.org/core/volume | "281"xsd:string |
| http://purl.uniprot.org/citations/16714282 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/16714282 |
| http://purl.uniprot.org/citations/16714282 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/16714282 |
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| http://purl.uniprot.org/uniprot/#_P52566-mappedCitation-16714282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16714282 |
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| http://purl.uniprot.org/uniprot/#_Q3UL78-mappedCitation-16714282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16714282 |
| http://purl.uniprot.org/uniprot/#_Q99JI7-mappedCitation-16714282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16714282 |
| http://purl.uniprot.org/uniprot/#_Q03135-mappedCitation-16714282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16714282 |
| http://purl.uniprot.org/uniprot/#_P60766-mappedCitation-16714282 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/16714282 |
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| http://purl.uniprot.org/uniprot/P49817 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/16714282 |
| http://purl.uniprot.org/uniprot/Q99819 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/16714282 |
| http://purl.uniprot.org/uniprot/Q03135 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/16714282 |