Identification and characterization of a leucine-rich repeat kinase 2 (LRRK2) consensus phosphorylation motif.

ABSTRACT: Mutations in LRRK2 (leucine-rich repeat kinase 2) have been identified as major genetic determinants of Parkinson's disease (PD). The most prevalent mutation, G2019S, increases LRRK2's kinase activity, therefore understanding the sites and substrates that LRRK2 phosphorylates is critical to understanding its role in disease aetiology. Since the physiological substrates of this kinase are unknown, we set out to reveal potential targets of LRRK2 G2019S by identifying its favored phosphorylation motif. A non-biased screen of an oriented peptide library elucidated F/Y-x-T-x-R/K as the core dependent substrate sequence. Bioinformatic analysis of the consensus phosphorylation motif identified several novel candidate substrates that potentially function in neuronal pathophysiology. Peptides corre

SUBMITTER: Pungaliya PP 

PROVIDER: S-EPMC2965117 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature