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Gloeckner, C.J. ; Kinkl, N. ; Schumacher, A. ; Braun, R.J. ; O'Neill, E.* ; Meitinger, T. ; Kolch, W.* ; Prokisch, H. ; Ueffing, M.

The parkinson disease causing LRRK2 mutation I2020T is associated with increased kinase activity.

Hum. Mol. Genet. 15, 223-232 (2006)
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Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal dominant late-onset Parkinson disease (PD). The LRRK2 protein consists of multiple domains and belongs to the Roco family, a novel group of the Ras/GTPase superfamily. Besides the GTPase (Roc) domain, it contains a predicted kinase domain, with homology to MAP kinase kinase kinases. Using cell fractionation and immunofluorescence microscopy, we show that LRRK2 is localized in the cytoplasm and is associated with cellular membrane structures. The purified LRRK2 protein demonstrates autokinase activity. The disease-associated I2020T mutant shows a significant increase in autophosphorylation of similar to 40% in comparison to wild-type protein in vitro. This suggests that the pathology of PD caused by the I2020T mutation is associated with an increase rather than a loss in LRRK2 kinase activity.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords POLYACRYLAMIDE-GELS; TYROSINE KINASES; RAF-1 KINASE; DAP-KINASE; ACTIVATION; PHOSPHORYLATION; PROTEINS; STRESS; HSP90; DJ-1
ISSN (print) / ISBN 0964-6906
e-ISSN 1460-2083
Journal Human Molecular Genetics
Quellenangaben Volume: 15, Issue: 2, Pages: 223-232 Article Number: , Supplement: ,
Publisher Oxford University Press
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)