The role of (auto)-phosphorylation in the complex activation mechanism of LRRK2


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Athanasopoulos P. S. , Heumann R., Kortholt A.

BIOLOGICAL CHEMISTRY, vol.399, no.7, pp.643-647, 2018 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 399 Issue: 7
  • Publication Date: 2018
  • Doi Number: 10.1515/hsz-2017-0332
  • Journal Name: BIOLOGICAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.643-647
  • Keywords: GTPase, kinase, neuronal degeneration, Parkinson's disease, phosphatases, DISEASE-ASSOCIATED MUTATIONS, SYNAPTIC VESICLE TRAFFICKING, PARKINSONS-DISEASE, KINASE-ACTIVITY, GTP-BINDING, PHOSPHORYLATION, PENETRANCE, PHENOTYPE, DISRUPTS

Abstract

Mutations in human leucine-rich-repeat kinase 2 (LRRK2) have been found to be the most frequent cause of late-onset Parkinson's Disease (PD). LRRK2 is a large protein with two enzymatic domains, a GTPase and a kinase domain. A cluster of (auto)-phosphorylation sites within the N-terminus of LRRK2 have been shown to be crucial for the localization of LRRK2 and is important for PD pathogenesis. In addition, phosphorylation of sites within the G-domain of the protein affect GTPase activity. Here we discuss the role of these (auto)-phosphorylation sites of LRRK2 and their regulation by phosphatases and upstream kinases.