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http://purl.uniprot.org/citations/19620781http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19620781http://www.w3.org/2000/01/rdf-schema#comment"The anorexigenic neuromodulator alpha-melanocyte-stimulating hormone (alpha-MSH; referred to here as alpha-MSH1-13) undergoes extensive posttranslational processing, and its in vivo activity is short lived due to rapid inactivation. The enzymatic control of alpha-MSH1-13 maturation and inactivation is incompletely understood. Here we have provided insight into alpha-MSH1-13 inactivation through the generation and analysis of a subcongenic mouse strain with reduced body fat compared with controls. Using positional cloning, we identified a maximum of 6 coding genes, including that encoding prolylcarboxypeptidase (PRCP), in the donor region. Real-time PCR revealed a marked genotype effect on Prcp mRNA expression in brain tissue. Biochemical studies using recombinant PRCP demonstrated that PRCP removes the C-terminal amino acid of alpha-MSH1-13, producing alpha-MSH1-12, which is not neuroactive. We found that Prcp was expressed in the hypothalamus in neuronal populations that send efferents to areas where alpha-MSH1-13 is released from axon terminals. The inhibition of PRCP activity by small molecule protease inhibitors administered peripherally or centrally decreased food intake in both wild-type and obese mice. Furthermore, Prcp-null mice had elevated levels of alpha-MSH1-13 in the hypothalamus and were leaner and shorter than the wild-type controls on a regular chow diet; they were also resistant to high-fat diet-induced obesity. Our results suggest that PRCP is an important component of melanocortin signaling and weight maintenance via control of active alpha-MSH1-13 levels."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.org/dc/terms/identifier"doi:10.1172/jci37209"xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Gao Q."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Wardlaw S.L."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Warden C.H."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Liu Z.W."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Diano S."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Gao X.B."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Coppola A."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Haus K.A."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Mahdi F."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Perroud B."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Schmaier A.H."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Shariat-Madar Z."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Wallingford N."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Diament A."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/author"Gyengesi E."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/name"J Clin Invest"xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/pages"2291-2303"xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/title"Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents."xsd:string
http://purl.uniprot.org/citations/19620781http://purl.uniprot.org/core/volume"119"xsd:string
http://purl.uniprot.org/citations/19620781http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19620781
http://purl.uniprot.org/citations/19620781http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19620781