http://purl.uniprot.org/citations/19620781 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/19620781 | http://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/19620781 | http://purl.org/dc/terms/identifier | "doi:10.1172/jci37209"xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Gao Q."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Wardlaw S.L."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Warden C.H."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Liu Z.W."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Diano S."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Gao X.B."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Coppola A."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Haus K.A."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Mahdi F."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Perroud B."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Schmaier A.H."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Shariat-Madar Z."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Wallingford N."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Diament A."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/author | "Gyengesi E."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/date | "2009"xsd:gYear |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/name | "J Clin Invest"xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/pages | "2291-2303"xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/title | "Prolylcarboxypeptidase regulates food intake by inactivating alpha-MSH in rodents."xsd:string |
http://purl.uniprot.org/citations/19620781 | http://purl.uniprot.org/core/volume | "119"xsd:string |
http://purl.uniprot.org/citations/19620781 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/19620781 |
http://purl.uniprot.org/citations/19620781 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/19620781 |