http://purl.uniprot.org/citations/22012985 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/22012985 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
http://purl.uniprot.org/citations/22012985 | http://www.w3.org/2000/01/rdf-schema#comment | "Mutations in the leucine-rich repeat kinase-2 (LRRK2) gene cause late-onset Parkinson's disease, but its physiological function has remained largely unknown. Here we report that LRRK2 activates a calcium-dependent protein kinase kinase-β (CaMKK-β)/adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway which is followed by a persistent increase in autophagosome formation. Simultaneously, LRKR2 overexpression increases the levels of the autophagy receptor p62 in a protein synthesis-dependent manner, and decreases the number of acidic lysosomes. The LRRK2-mediated effects result in increased sensitivity of cells to stressors associated with abnormal protein degradation. These effects can be mimicked by the lysosomal Ca(2+)-mobilizing messenger nicotinic acid adenine dinucleotide phosphate (NAADP) and can be reverted by an NAADP receptor antagonist or expression of dominant-negative receptor constructs. Collectively, our data indicate a molecular mechanism for LRRK2 deregulation of autophagy and reveal previously unidentified therapeutic targets."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/name | "Hum. Mol. Genet."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/name | "Hum. Mol. Genet."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddr481"xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddr481"xsd:string |
http://purl.uniprot.org/citations/22012985 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22012985 |
http://purl.uniprot.org/citations/22012985 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22012985 |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Patel S."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Patel S."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Woodman P.G."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Woodman P.G."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Churamani D."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Churamani D."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Churchill G.C."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Churchill G.C."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Bloor-Young D."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Bloor-Young D."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Gomez-Suaga P."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Gomez-Suaga P."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Hilfiker S."xsd:string |
http://purl.uniprot.org/citations/22012985 | http://purl.uniprot.org/core/author | "Hilfiker S."xsd:string |