HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Institute for Genetic Medicine >
Peer-reviewed Journal Articles, etc >

Functional characterization of lysosomal interaction of Akt with VRK2

This item is licensed under: Creative Commons Attribution 4.0 International

Files in This Item:
41388_2018_330_MOESM1_ESM.docxSupplemental data and legend72.11 kBMicrosoft Word XMLView/Open
41388_2018_330_MOESM2_ESM.pdfSupplemental data 1747.63 kBPDFView/Open
41388_2018_330_MOESM3_ESM.pdfSupplemental data 282.06 kBPDFView/Open
41388_2018_330_MOESM4_ESM.pdfSupplemental data 3830.14 kBPDFView/Open
41388_2018_330_MOESM5_ESM.pdfSupplemental data 4723.77 kBPDFView/Open
41388_2018_330_MOESM6_ESM.pdfSupplemental data 5854.07 kBPDFView/Open
41388_2018_330_MOESM7_ESM.pdfSupplemental data 6949.38 kBPDFView/Open
41388_2018_330_MOESM8_ESM.pdfSupplemental data 7475.89 kBPDFView/Open
s41388-018-0330-0.pdf7.07 MBPDFView/Open
Please use this identifier to cite or link to this item:

Title: Functional characterization of lysosomal interaction of Akt with VRK2
Authors: Hirata, Noriyuki Browse this author
Suizu, Futoshi Browse this author →KAKEN DB
Matsuda-Lennikov, Mami Browse this author
Tanaka, Tsutomu Browse this author
Edamura, Tatsuma Browse this author
Ishigaki, Satoko Browse this author
Donia, Thoria Browse this author
Lithanatudom, Pathrapol Browse this author
Obuse, Chikashi Browse this author
Iwanaga, Toshihiko Browse this author →KAKEN DB
Noguchi, Masayuki Browse this author →KAKEN DB
Issue Date: 4-Oct-2018
Publisher: Nature Publishing Group
Journal Title: Oncogene
Volume: 37
Issue: 40
Start Page: 5367
End Page: 5386
Publisher DOI: 10.1038/s41388-018-0330-0
Abstract: Serine-threonine kinase Akt (also known as PKB, protein kinase B), a core intracellular mediator of cell survival, is involved in various human cancers and has been suggested to play an important role in the regulation of autophagy in mammalian cells. Nonetheless, the physiological function of Akt in the lysosomes is currently unknown. We have reported previously that PtdIns (3)P-dependent lysosomal accumulation of the Akt-Phafin2 complex is a critical step for autophagy induction. Here, to characterize the molecular function of activated Akt in the lysosomes in the process of autophagy, we searched for the molecules that interact with the Akt complex at the lysosomes after induction of autophagy. By time-of-flight-mass spectrometry (TOF/MS) analysis, kinases of the VRK family, a unique serine-threonine family of kinases in the human kinome, were identified. VRK2 interacts with Akt1 and Akt2, but not with Akt3; the C terminus of Akt and the N terminus of VRK2 facilitate the interaction of Akt and VRK2 in mammalian cells. The kinase-dead form of VRK2A (KD VRK2A) failed to interact with Akt in coimmunoprecipitation assays. Bimolecular fluorescence complementation (BiFC) experiments showed that, in the lysosomes, Akt interacted with VRK2A but not with VRK2B or KD VRK2A. Immunofluorescent assays revealed that VRK2 and phosphorylated Akt accumulated in the lysosomes after autophagy induction. WT VRK2A, but not KD VRK2A or VRK2B, facilitated accumulation of phosphorylated Akt in the lysosomes. Downregulation of VRK2 abrogated the lysosomal accumulation of phosphorylated Akt and impaired nuclear localization of TFEB; these events coincided to inhibition of autophagy induction. The VRK2-Akt complex is required for control of lysosomal size, acidification, bacterial degradation, and for viral replication. Moreover, lysosomal VRK2-Akt controls cellular proliferation and mitochondria) outer-membrane stabilization. Given the roles of autophagy in the pathogenesis of human cancer, the current study provides a novel insight into the oncogenic activity of VRK2-Akt complexes in the lysosomes via modulation of autophagy.
Type: article
Appears in Collections:遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 野口 昌幸

Export metadata:

OAI-PMH ( junii2 , jpcoar )

MathJax is now OFF:


Feedback - Hokkaido University