Negative Regulation of Vps34 by Cdk Mediated Phosphorylation
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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier B.V.
2015
|
| Online Access: | http://hdl.handle.net/1721.1/96110 https://orcid.org/0000-0003-1262-0592 |
| _version_ | 1826212041392652288 |
|---|---|
| author | Furuya, Tsuyoshi Kim, Minsu Lipinski, Marta Li, Juying Kim, Dohoon Lu, Tao Shen, Yong Rameh, Lucia Yankner, Bruce Tsai, Li-Huei Yuan, Junying |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Furuya, Tsuyoshi Kim, Minsu Lipinski, Marta Li, Juying Kim, Dohoon Lu, Tao Shen, Yong Rameh, Lucia Yankner, Bruce Tsai, Li-Huei Yuan, Junying |
| author_sort | Furuya, Tsuyoshi |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:15:31Z |
| format | Article |
| id | mit-1721.1/96110 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:15:31Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/961102022-09-29T13:41:24Z Negative Regulation of Vps34 by Cdk Mediated Phosphorylation Furuya, Tsuyoshi Kim, Minsu Lipinski, Marta Li, Juying Kim, Dohoon Lu, Tao Shen, Yong Rameh, Lucia Yankner, Bruce Tsai, Li-Huei Yuan, Junying Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Picower Institute for Learning and Memory Kim, Dohoon Tsai, Li-Huei 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. National Institute on Aging (PO1 AG027916) National Institute on Aging (R37 AG 012859) Samsung (Firm) (Scholarship from South Korea) 2015-03-20T14:18:54Z 2015-03-20T14:18:54Z 2010-05 2009-10 Article http://purl.org/eprint/type/JournalArticle 10972765 http://hdl.handle.net/1721.1/96110 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. https://orcid.org/0000-0003-1262-0592 en_US http://dx.doi.org/10.1016/j.molcel.2010.05.009 Molecular Cell 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. application/pdf Elsevier B.V. Elsevier |
| spellingShingle | Furuya, Tsuyoshi Kim, Minsu Lipinski, Marta Li, Juying Kim, Dohoon Lu, Tao Shen, Yong Rameh, Lucia Yankner, Bruce Tsai, Li-Huei Yuan, Junying Negative Regulation of Vps34 by Cdk Mediated Phosphorylation |
| title | Negative Regulation of Vps34 by Cdk Mediated Phosphorylation |
| title_full | Negative Regulation of Vps34 by Cdk Mediated Phosphorylation |
| title_fullStr | Negative Regulation of Vps34 by Cdk Mediated Phosphorylation |
| title_full_unstemmed | Negative Regulation of Vps34 by Cdk Mediated Phosphorylation |
| title_short | Negative Regulation of Vps34 by Cdk Mediated Phosphorylation |
| title_sort | negative regulation of vps34 by cdk mediated phosphorylation |
| url | http://hdl.handle.net/1721.1/96110 https://orcid.org/0000-0003-1262-0592 |
| work_keys_str_mv | AT furuyatsuyoshi negativeregulationofvps34bycdkmediatedphosphorylation AT kimminsu negativeregulationofvps34bycdkmediatedphosphorylation AT lipinskimarta negativeregulationofvps34bycdkmediatedphosphorylation AT lijuying negativeregulationofvps34bycdkmediatedphosphorylation AT kimdohoon negativeregulationofvps34bycdkmediatedphosphorylation AT lutao negativeregulationofvps34bycdkmediatedphosphorylation AT shenyong negativeregulationofvps34bycdkmediatedphosphorylation AT ramehlucia negativeregulationofvps34bycdkmediatedphosphorylation AT yanknerbruce negativeregulationofvps34bycdkmediatedphosphorylation AT tsailihuei negativeregulationofvps34bycdkmediatedphosphorylation AT yuanjunying negativeregulationofvps34bycdkmediatedphosphorylation |