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?

Gillardon F, Kremmer E, Froehlich T, Ueffing M, Hengerer B, Gloeckner CJ.
Journal   J Neurosci Methods
Analytes Measured  
Matrix Tested   Cell lysates
Year   2013
Volume   214
Page Numbers   62-68
Application   Phosphoproteins
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.

View Publications
Browse Our Products

By Analytes
By Applications
Customer Service/Orders

Scientific/Technical Support

Instrument Support

Company Headquarters