| http://purl.uniprot.org/citations/26930193 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26930193 | http://www.w3.org/2000/01/rdf-schema#comment | "BackgroundRecent studies have linked certain single nucleotide polymorphisms in the leucine-rich repeat kinase 2 (LRRK2) gene with Parkinson's disease (PD). Among the mutations, LRRK2 c.4883G>C (R1628P) variant was identified to have a significant association with the risk of PD in ethnic Han-Chinese populations. But the molecular pathological mechanisms of R1628P mutation in PD is still unknown.Principle findingsUnlike other LRRK2 mutants in the Roc-COR-Kinase domain, the R1628P mutation didn't alter the LRRK2 kinase activity and promote neuronal death directly. LRRK2 R1628P mutation increased the binding affinity of LRRK2 with Cyclin-dependent kinase 5 (Cdk5). Interestingly, R1628P mutation turned its adjacent amino acid residue S1627 on LRRK2 protein to a novel phosphorylation site of Cdk5, which could be defined as a typical type II (+) phosphorylation-related single nucleotide polymorphism. Importantly, we showed that the phosphorylation of S1627 by Cdk5 could activate the LRRK2 kinase, and neurons ectopically expressing R1628P displayed a higher sensitivity to 1-methyl-4-phenylpyridinium, a bioactive metabolite of environmental toxin MPTP, in a Cdk5-dependent manner.ConclusionOur data indicate that Parkinson-related LRRK2 mutation R1628P leads to Cdk5 phosphorylation of LRRK2 at S1627, which would upregulate the kinase activity of LRRK2 and consequently cause neuronal death."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0149739"xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/author | "Wang Q."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/author | "Zhang P."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/author | "Tian B."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/author | "Shu Y."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/author | "Jiao F."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/author | "Ming J."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/pages | "e0149739"xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/title | "Parkinson-Related LRRK2 Mutation R1628P Enables Cdk5 Phosphorylation of LRRK2 and Upregulates Its Kinase Activity."xsd:string |
| http://purl.uniprot.org/citations/26930193 | http://purl.uniprot.org/core/volume | "11"xsd:string |
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