Title: The Parkinson's disease kinase LRRK2 autophosphorylates its GTPase domain at multiple sites
Authors: Greggio, Elisa *
Taymans, Jean-Marc *
Zhen, Eugene Yuejun
Ryder, John
Vancraenenbroeck, Renée
Beilina, Alexandra
Sun, Peng
Deng, Junpeng
Jaffe, Howard
Baekelandt, Veerle
Merchant, Kalpana
Cookson, Mark R # ×
Issue Date: Nov-2009
Publisher: Academic Press
Series Title: Biochemical and Biophysical Research Communications vol:389 issue:3 pages:449-454
Abstract: Mutations in leucine-rich repeat kinase 2 (LRRK2) are a common cause of inherited Parkinson's disease (PD). The protein is large and complex, but pathogenic mutations cluster in a region containing GTPase and kinase domains. LRRK2 can autophosphorylate in vitro within a dimer pair, although the significance of this reaction is unclear. Here, we mapped the sites of autophosphorylation within LRRK2 and found several potential phosphorylation sites within the GTPase domain. Using mass spectrometry, we found that Thr1343 is phosphorylated and, using kinase dead versions of LRRK2, show that this is an autophosphorylation site. However, we also find evidence for additional sites in the GTPase domain and in other regions of the protein suggesting that there may be multiple autophosphorylation sites within LRRK2. These data suggest that the kinase and GTPase activities of LRRK2 may exhibit complex autoregulatory interdependence.
ISSN: 0006-291X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Research Group for Neurobiology and Gene Therapy
Biochemistry, Molecular and Structural Biology Section
* (joint) first author
× corresponding author
# (joint) last author

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