Global Experts Meeting on Infectious Diseases
Title: Functional interaction of Akt with VRK2 at lysosomes controls infectious diseases by modulation of autophagy
Biography: Masayuki Noguchi
Lysosome is known to degrade phagocytosed infectious particles through endocytic and autophagic pathways. Serine threonine kinase Akt (also known as PKB, protein kinase B), a core intracellular survival mediator, which underlies various human diseases, has been suggested to play an important role in the regulation of autophagy in mammalian cells. However, defined physiological function of Akt at the lysosome is currently unknown. We have reported that PtdIns(3)P-dependent lysosomal accumulation of Akt-Phafin2 complex is a critical step for autophagy induction. To characterize molecular function of activated Akt at the lysosome in the process of autophagy, we searched for the molecules which interact with Akt complex at the lysosome after induction of autophagy. By TOF/MS analysis of immune complexes of Akt at the lysosome after induction of autophagy, VRK (Vaccinia Related Protein Kinase) family kinases, a unique serine threonine family of kinases in the human kinome, were identified. Bimolecular fluorescence complementation (BiFC) experiments showed that Akt interacted with VRK2 at the lysosomes. Immunofluorescent studies showed that VRK2 and phosphorylated Akt are accumulated at the lysosome after autophagy induction. VRK2 facilitates accumulation of phosphorylated Akt at the lysosome. Inhibition of VRK2 abrogated the lysosomal accumulation of phosphorylated Akt which coincides with inhibition of autophagy induction. VRK2-Akt is required for controlling lysosomal size, acidification due to insufficient biogenesis of the lysosome.