Raptor is Phosphorylated by Cdc2 During Mitosis

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Raptor is Phosphorylated by Cdc2 During Mitosis

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dc.contributor.author Gwinn, Dana M.
dc.contributor.author Shaw, Reuben J.
dc.contributor.author Asara, John M
dc.date.accessioned 2011-04-27T00:26:52Z
dc.date.issued 2010
dc.identifier.citation Gwinn, Dana M., John M. Asara, and Reuben J. Shaw. 2010. Raptor is phosphorylated by cdc2 during mitosis. PLoS ONE 5(2): e9197. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4878053
dc.description.abstract Background: The appropriate control of mitotic entry and exit is reliant on a series of interlocking signaling events that coordinately drive the biological processes required for accurate cell division. Overlaid onto these signals that promote orchestrated cell division are checkpoints that ensure appropriate mitotic spindle formation, a lack of DNA damage, kinetochore attachment, and that each daughter cell has the appropriate complement of DNA. We recently discovered that AMP-activated protein kinase (AMPK) modulates the G2/M phase of cell cycle progression in part through its suppression of mammalian target of rapamycin (mTOR) signaling. AMPK directly phosphorylates the critical mTOR binding partner raptor inhibiting mTORC1 (mTOR-raptor rapamycin sensitive mTOR kinase complex 1). As mTOR has been previously tied to mitotic control, we examined further how raptor may contribute to this process. Methodology/Principal Findings: We have discovered that raptor becomes highly phosphorylated in cells in mitosis. Utilizing tandem mass spectrometry, we identified a number of novel phosphorylation sites in raptor, and using phospho-specific antibodies demonstrated that raptor becomes phosphorylated on phospho-serine/threonine-proline sites in mitosis. A combination of site-directed mutagenesis in a tagged raptor cDNA and analysis with a series of new phospho-specific antibodies generated against different sites in raptor revealed that Serine 696 and Threonine 706 represent two key sites in raptor phosphorylated in mitosis. We demonstrate that the mitotic cyclin-dependent kinase cdc2/CDK1 is the kinase responsible for phosphorylating these sites, and its mitotic partner Cyclin B efficiently coimmunoprecipitates with raptor in mitotic cells. Conclusions/Significance: This study demonstrates that the key mTOR binding partner raptor is directly phosphorylated during mitosis by cdc2. This reinforces previous studies suggesting that mTOR activity is highly regulated and important for mitotic progression, and points to a direct modulation of the mTORC1 complex during mitosis. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0009197 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2820552/pdf/ en_US
dash.license LAA
dc.subject biochemistry en_US
dc.subject cell signaling and trafficking structures en_US
dc.subject cell biology en_US
dc.subject cell growth and division en_US
dc.subject cell signaling en_US
dc.title Raptor is Phosphorylated by Cdc2 During Mitosis en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Asara, John M
dc.date.available 2011-04-27T00:26:52Z
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US

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