assays for pten-induced novel kinase 1 (PINK1) and Leucine-Rich repeat kinase 2 (LRRK2), kinases associated with parkinson’s disease

Abstract

PTEN-induced novel kinase 1 (PINK1) and leucine-rich repeat kinase 2 (LRRK2) are two protein kinases associated with recessive and dominant forms of parkinsonism, respectively. Mutations in PINK1 cause loss of protein function whereas mutations in LRRK2 are less easily de fined but, in some cases, may cause increased kinase activity. Furthermore, LRRK2 kinase activity is being explored as a therapeutic target in PD. Therefore, in both the cases of PINK1 and LRRK2, measuring kinase activity is important but is complicated by the problem that convincing physiological substrates of the two proteins have not yet been found. In this chapter, we will describe in detail the protocols we use in our lab to measure activity and related functions of these two kinases.