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LRRK2 Kinase Activity is Dependent on Dimerization
Author(s) -
Sen Saurabh,
West Andrew
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.681.14
Subject(s) - lrrk2 , kinase , protein kinase domain , leucine rich repeat , cyclin dependent kinase 9 , map3k7 , biology , chemistry , protein kinase a , microbiology and biotechnology , mitogen activated protein kinase kinase , biochemistry , gene , mutation , mutant
Current therapies for Parkinson's disease (PD) fail to slow the onset or progression of disease. Pathogenic missense mutations in the PARK8 locus encoding the leucine‐rich repeat kinase 2 ( LRRK2 ) gene cause late‐onset disease that mimics the clinical and neurochemical aspects of idiopathic disease. The most common LRRK2 mutations occur in the kinase domain and enhance both kinase activity and toxicity in vitro. LRRK2 represents a clear target for modulation by small molecule kinase inhibitors that may provide neuroprotection in patients that harbor LRRK2 mutations and possibly PD cases without LRRK2 mutations. Through the biochemical characterization of LRRK2 protein, we find that kinase activity is dependent on dimerization whereas further oligomerization results in a loss of activity. We develop a Bimolecular Fluorescence (BiFC) assay based on eGFP fluorescence dependent on protein dimerization. Cell‐based LRRK2 kinase assays should hasten the identification of specific and effective LRRK2 inhibitors.