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Title

Cellular effects mediated by pathogenic LRRK2: homing in on Rab-mediated processes

AuthorsMadero-Pérez, Jesús; Fdez, E.; Fernández, Belén; Lara Ordonez, Antonio J.; Blanca Ramírez, Marian; Romo Lozano, María; Rivero-Rios, Pilar; Hilfiker, Sabine
KeywordsGDI
GEF
REP
Rab protein
leucine-rich repeat kinase
vesicular trafficking
Issue Date8-Feb-2017
PublisherPortland Press
CitationBiochemical Society Transactions
AbstractLeucine-rich repeat kinase 2 (LRRK2) is a key player in the pathogenesis of Parkinson's disease. Mutations in LRRK2 are associated with increased kinase activity that correlates with cytotoxicity, indicating that kinase inhibitors may comprise promising disease-modifying compounds. However, before embarking on such strategies, detailed knowledge of the cellular deficits mediated by pathogenic LRRK2 in the context of defined and pathologically relevant kinase substrates is essential. LRRK2 has been consistently shown to impair various intracellular vesicular trafficking events, and recent studies have shown that LRRK2 can phosphorylate a subset of proteins that are intricately implicated in those processes. In light of these findings, we here review the link between cellular deficits in intracellular trafficking pathways and the LRRK2-mediated phosphorylation of those newly identified substrates.
Publisher version (URL)http://dx.doi.org/10.1042/BST20160392
URIhttp://hdl.handle.net/10261/182924
DOI10.1042/BST20160392
ISSN0300-5127
E-ISSN1470-8752
Appears in Collections:(IPBLN) Artículos
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