raptor is phosphorylated by cdc2 during mitosis在有丝分裂猛禽被cdc2磷酸化.pdfVIP

Raptor is Phosphorylated by cdc2 during Mitosis 1 3,4 1,2 Dana M. Gwinn , John M. Asara , Reuben J. Shaw * 1 Molecular and Cell Biology Laboratory, Dulbecco Center for Cancer Research, La Jolla, California, United States of America, 2 Howard Hughes Medical Institute, Salk Institute for Biological Studies, La Jolla, California, United States of America, 3 Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America, 4 Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America 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 an