Much research has focused on understanding how mutations in a protein kinase termed LRRK2, predisposes to Parkinson’s disease. Most pathogenic mutations occur within the kinase domain (G2019S) and GTPase ROC/COR domain (R1441G and Y1699C) of LRRK2.
Recent studies undertaken in the Alessi, Mann and Pfeffer labs, have revealed that LRRK2 phosphorylates a group of Rab GTPase proteins including Rab29 (also known as Rab7L1), within the effector‐binding switch II motif. This enables Rab proteins to interact with new effectors including RILPL1 and RILPL2.
Mutations located within the kinase domain such as G2019S, directly stimulate protein kinase activity of LRRK2. …more