Negative Regulation of Vps34 by Cdk Mediated Phosphorylation
Author(s)
Furuya, Tsuyoshi; Kim, Minsu; Lipinski, Marta; Li, Juying; Kim, Dohoon; Lu, Tao; Shen, Yong; Rameh, Lucia; Yankner, Bruce; Tsai, Li-Huei; Yuan, Junying; ... Show more Show less
DownloadFuruya-2010-Negative Regulation.pdf (1.130Mb)
PUBLISHER_POLICY
Publisher Policy
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
Terms of use
Metadata
Show full item recordAbstract
Vacuolar protein sorting 34 (Vps34) complexes, the class III PtdIns3 kinase, specifically phosphorylate the D3 position of PtdIns to produce PtdIns3P. Vps34 is involved in the control of multiple key intracellular membrane trafficking pathways including endocytic sorting and autophagy. In mammalian cells, Vps34 interacts with Beclin 1, an ortholog of Atg6 in yeast, to regulate the production of PtdIns3P and autophagy. We show that Vps34 is phosphorylated on Thr159 by Cdk1, which negatively regulates its interaction with Beclin 1 during mitosis. Cdk5/p25, a neuronal Cdk shown to play a role in Alzheimer's disease, can also phosphorylate Thr159 of Vps34. Phosphorylation of Vps34 on Thr159 inhibits its interaction with Beclin 1. We propose that phosphorylation of Thr159 in Vps34 is a key regulatory mechanism that controls the class III PtdIns3 kinase activity in cell-cycle progression, development, and human diseases including neurodegeneration and cancers.
Date issued
2010-05Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences; Picower Institute for Learning and MemoryJournal
Molecular Cell
Publisher
Elsevier B.V.
Citation
Furuya, Tsuyoshi, Minsu Kim, Marta Lipinski, Juying Li, Dohoon Kim, Tao Lu, Yong Shen, et al. “Negative Regulation of Vps34 by Cdk Mediated Phosphorylation.” Molecular Cell 38, no. 4 (May 2010): 500–511. © 2010 Elsevier Inc.
Version: Final published version
ISSN
10972765