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| http://purl.uniprot.org/citations/15537656 | http://www.w3.org/2000/01/rdf-schema#comment | "In pancreatic beta cells, insulin granule exocytosis is regulated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor protein (SNAP) receptor) proteins, and this is coupled to cortical F-actin reorganization via the Rho family GTPase Cdc42 by an unknown mechanism. We investigated interactions among the target SNARE protein Syntaxin 1A and the vesicle-associated membrane SNARE protein (VAMP2) with Cdc42 and compared these structural interactions with their functional importance to glucose-stimulated insulin secretion in MIN6 beta cells. Subcellular fractionation analyses revealed a parallel redistribution of Cdc42 and VAMP2 from the granule fraction to the plasma membrane in response to glucose that temporally corresponded with the glucose-induced activation of Cdc42. Moreover, within these fractions Cdc42 and VAMP2 were found to co-immunoprecipitate under basal and glucose-stimulated conditions, suggesting that they moved as a complex. Furthermore, VAMP2 bound both GST-Cdc42-GTPgammaS and GST-Cdc42-GDP, indicating that the Cdc42-VAMP2 complex could form under both cytosolic GDP-bound Cdc42 and plasma membrane GTP-bound Cdc42 conformational conditions. In vitro binding analyses showed that VAMP2 bound directly to Cdc42 and that a heterotrimeric complex with Syntaxin 1A could also be formed. Deletion analyses of VAMP2 revealed that only the N-terminal 28 residues were required for Cdc42 binding. Expression of this 28-residue VAMP2 peptide in MIN6 beta cells resulted in the specific impairment of glucose-stimulated insulin secretion, indicating a functional importance for the Cdc42-VAMP2 interaction. Taken together, these data suggest a mechanism whereby glucose activates Cdc42 to induce the targeting of intracellular Cdc42-VAMP2-insulin granule complexes to Syntaxin 1A at the plasma membrane."xsd:string |
| http://purl.uniprot.org/citations/15537656 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m409528200"xsd:string |
| http://purl.uniprot.org/citations/15537656 | http://purl.uniprot.org/core/author | "Thurmond D.C."xsd:string |
| http://purl.uniprot.org/citations/15537656 | http://purl.uniprot.org/core/author | "Nevins A.K."xsd:string |
| http://purl.uniprot.org/citations/15537656 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15537656 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/15537656 | http://purl.uniprot.org/core/pages | "1944-1952"xsd:string |
| http://purl.uniprot.org/citations/15537656 | http://purl.uniprot.org/core/title | "A direct interaction between Cdc42 and vesicle-associated membrane protein 2 regulates SNARE-dependent insulin exocytosis."xsd:string |
| http://purl.uniprot.org/citations/15537656 | http://purl.uniprot.org/core/volume | "280"xsd:string |
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