title: LRRK2 GTPase dysfunction in the pathogenesis of Parkinson's disease.
abstract: Mutations in the LRRK2 (leucine-rich repeat kinase 2) gene are the most frequent genetic cause of PD (Parkinson's disease), and these mutations play important roles in sporadic PD. The LRRK2 protein contains GTPase and kinase domains and several protein-protein interaction domains. The kinase and GTPase activity of LRRK2 seem to be important in regulating LRRK2-dependent cellular signalling pathways. LRRK2's GTPase and kinase domains may reciprocally regulate each other to direct LRRK2's ultimate function. Although most LRRK2 investigations are centred on LRRK2's kinase activity, the present review focuses on the function of LRRK2's GTPase activity in LRRK2 physiology and pathophysiology.
authors.affiliation: Neuroregeneration and Stem Cell Programs, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Yulan
authors.initials: Y
authors.lastname: Xiong
authors.forename: Valina L
authors.initials: VL
authors.lastname: Dawson
authors.forename: Ted M
authors.initials: TM
authors.lastname: Dawson
mesh_terms: D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D009154:Mutation; D010300:Parkinson Disease / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; D020558:GTP Phosphohydrolases