Chemical Biology of the Cell | Small Molecule Chemistry | Motor Systems | Cell Signaling & Trafficking Structures | Biomacromolecule-Ligand Interactions | Movement Disorders
High throughput screening of small molecules that inhibit LRRK2 phosphorylation on serine 935 reveals novel inhibitors and cellular pathways that affect LRRK2
Spencer B Hermanson, Coby B Carlson, Steven M Riddle, Jing Zhao, Kun Bi, R Jeremy Nichols*
*Corresponding author: R Jeremy Nichols
The Parkinson's Institute, Sunnyvale, CA, USA
F1000Posters 2012, 3: 561 (poster) [English]
Poster [603.19 KB]
Presented at
Biochemical Society 2012 - LRRK2: Function and Dysfunction meeting ,
28 - 30 Mar 2012, P025
The leucine rich repeat kinase (LRRK) is found frequently mutated in familial Parkinson’s disease (PD). LRRK2 is phosphorylated on a cluster of serine residues (serines 910/935/955 and 973) in a manner dependent on LRRK2 kinase activity. These sites are also found dephosphorylated in the context of several pathogenic PD mutations. We developed a high-throughput screening compatible LanthaScreen assay to screen for compounds that inhibit LRRK2 phosphorylation at Ser935.
We identified several direct inhibitors of LRRK2 as well as other compounds that inhibit LRRK2 phosphorylation but not kinase activity. We identified several kinases able to phosphorylate LRRK2 in vitro. We also followed these results and demonstrated that TLR agonists can increase the phosphorylation of Ser935.
Corresponding author R Jeremy Nichols is a consultant for LifeTechnologies TM.
Michael J Fox Foundation, LRRK2 Biology
Brin/Wojcicki Foundation, LRRK2 Biology
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