LRRK2 directly phosphorylates Akt1 as a possible physiological substrate: Impairment of the kinase activity by Parkinson's disease-associated mutations

► We found that LRRK2 directly phosphorylated Akt1 at Ser473. ► The knockdown of LRRK2 resulted in a marked reduction of phospho-Akt1 at Ser473. ► The R1441C, G2019S, and I2020T mutant LRRK2 exhibited reduced interaction with, and phosphorylation of, Akt1. ► Akt1 is one of the physiological substrates of LRRK2.