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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Basseres, Daniela S. Van Dyke, Terry Ebbs, Aaron Baldwin, Albert S. Dan, Han C. Pasparakis, Manolis |
| Description | Author Affiliation: Dan HC ( From the Lineberger Comprehensive Cancer Center University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, Maryland 21201.); Ebbs A ( From the Lineberger Comprehensive Cancer Center University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.); Pasparakis M ( Institute for Genetics University of Cologne, Cologne, Germany.); Van Dyke T ( Mouse Cancer Genetics Program, NCI, National Institutes of Health, Frederick, Maryland 21702, and.); Basseres DS ( From the Lineberger Comprehensive Cancer Center University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599.); Baldwin AS ( From the Lineberger Comprehensive Cancer Center University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, abaldwin@med.unc.edu.) |
| Abstract | The serine/threonine protein kinase Akt promotes cell survival, growth, and proliferation through phosphorylation of different downstream substrates. A key effector of Akt is the mammalian target of rapamycin (mTOR). Akt is known to stimulate mTORC1 activity through phosphorylation of tuberous sclerosis complex 2 (TSC2) and PRAS40, both negative regulators of mTOR activity. We previously reported that IκB kinase (IKK ), a component of the kinase complex that leads to NF-κB activation, plays an important role in promoting mTORC1 activity downstream of activated Akt. Here, we demonstrate IKK -dependent regulation of mTORC1 using multiple PTEN null cancer cell lines and an animal model with deletion of IKK . Importantly, IKK is shown to phosphorylate mTOR at serine 1415 in a manner dependent on Akt to promote mTORC1 activity. These results demonstrate that IKK is an effector of Akt in promoting mTORC1 activity. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 36 |
| Volume Number | 289 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2014-09-05 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | I-kappa B Kinase Metabolism Multiprotein Complexes Proto-Oncogene Proteins C-akt TOR Serine-Threonine Kinases Adaptor Proteins, Signal Transducing Animals Cell Line, Tumor Cell Proliferation Cells, Cultured Enzyme Activation HEK293 Cells HeLa Cells Genetics Immunoblotting Mice, Knockout Mutation Phosphorylation Protein Binding RNA Interference Serine Tumor Suppressor Proteins Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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