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Gillardon, F.* ; Kremmer, E. ; Froehlich, T.* ; Ueffing, M. ; Hengerer, B.* ; Gloeckner, C.J.

ATP-competitive LRRK2 inhibitors interfere with monoclonal antibody binding to the kinase domain of LRRK2 under native conditions. A method to directly monitor the active conformation of LRRK2?

J. Neurosci. Methods 214, 62-68 (2013)
DOI PMC
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease. LRRK2 kinase activity is required for toxicity in neuronal cell cultures suggesting that selective kinase inhibitors may prevent neurodegeneration in patients. Directly monitoring LRRK2 activity in cells would be advantageous for the development of small molecule LRRK2 inhibitors. Here, we demonstrate that a monoclonal anti-LRRK2 antibody directed against the activation segment binds less efficiently to native LRRK2 protein in the presence of ATP-competitive LRRK2 inhibitors. Since kinase inhibitors prevent autophosphorylation and refolding of the activation segment, we hypothesize that the antibody preferentially binds to the active conformation of LRRK2 under native conditions.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter LRRK2; Kinase Domain ; Activation Segment ; Conformation ; Antibody ; Immunoprecipitation; Parkinsons-disease ; Cytoplasmic Localization ; Protein-kinases ; Leucine-rich-repeat-kinase-2 ; Autophosphorylation ; Phosphorylation ; Stability
Sprache englisch
Veröffentlichungsjahr 2013
HGF-Berichtsjahr 2013
ISSN (print) / ISBN 0165-0270
e-ISSN 1872-678X
Zeitschrift Journal of Neuroscience Methods
Quellenangaben Band: 214, Heft: 1, Seiten: 62-68 Artikelnummer: , Supplement: ,
Verlag Elsevier
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
Institute of Molecular Immunology (IMI)
POF Topic(s) 30203 - Molecular Targets and Therapies
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Enabling and Novel Technologies
Immune Response and Infection
PSP-Element(e) G-505700-001
G-501793-001
PubMed ID 23318290
DOI 10.1016/j.jneumeth.2012.12.015
WOS ID WOS:000315757000009
Scopus ID 84873431777
Erfassungsdatum 2013-02-26
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