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http://purl.uniprot.org/citations/26505901http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/26505901http://www.w3.org/2000/01/rdf-schema#comment"Type 2 Diabetes Mellitus with insulin resistance, pancreatic β cell dysfunction, and hepatic glucose overproduction is increasing in epidemic proportions worldwide. G protein-coupled receptor 40 (GPR40), a clinically proven anti-diabetic drug target, is mainly expressed in pancreatic β cells and insulin-secreting cell lines. Long chain fatty acids (LCFA) increase intracellular calcium concentration and amplify glucose-stimulated insulin secretion by activating GPR40. Here we report that the arginine 104 (R104) is critical for the normal function of GPR40. Mutation of R104 to Proline (R104P) results in complete loss of the receptor function. Linoleic acid, ligand of GPR40, could not elicit calcium increase and ERK phosphorylation in cells expressing this mutant receptor. Further study indicated the R104P mutation reduces cell surface localization of GPR40 without affecting the expression of the protein. The small portion of GPR40 R104P mutant that is still located on the membrane has no physiological function, and does not internalize in response to linoleic acid stimulation. These data demonstrate that R104 in GPR40 is critically involved in the normal receptor functions. Interestingly, R104P is a registered single-nucleotide polymorphism of GPR40. The relationship of this GPR40 variant and type 2 diabetes warrants further investigation."xsd:string
http://purl.uniprot.org/citations/26505901http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0141303"xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/author"Li J."xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/author"Guo S."xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/author"Zhang J."xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/author"Zhang S."xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/pages"e0141303"xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/title"A Single Amino Acid Mutation (R104P) in the E/DRY Motif of GPR40 Impairs Receptor Function."xsd:string
http://purl.uniprot.org/citations/26505901http://purl.uniprot.org/core/volume"10"xsd:string
http://purl.uniprot.org/citations/26505901http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/26505901
http://purl.uniprot.org/citations/26505901http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/26505901
http://purl.uniprot.org/uniprot/#_A5Z1T7-mappedCitation-26505901http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26505901
http://purl.uniprot.org/uniprot/#_Q0IJ71-mappedCitation-26505901http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26505901
http://purl.uniprot.org/uniprot/#_O14842-mappedCitation-26505901http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/26505901
http://purl.uniprot.org/uniprot/A5Z1T7http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/26505901
http://purl.uniprot.org/uniprot/Q0IJ71http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/26505901
http://purl.uniprot.org/uniprot/O14842http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/26505901