The DOI matches its Crossref record; 28 of the 28 references it cites were found in a registry or an index.
Phosphorylation and Regulation of Akt/PKB by the Rictor-mTOR Complex
Abstract
Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr 308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser 473 within the carboxyl-terminal hydrophobic motif by an unknown kinase. We show that in Drosophila and human cells the target of rapamycin (TOR) kinase and its associated protein rictor are necessary for Ser 473 phosphorylation and that a reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB effector. The rictor-mTOR complex directly phosphorylated Akt/PKB on Ser 473 in vitro and facilitated Thr 308 phosphorylation by PDK1. Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation.
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“Akt is also phosphorylated within the carboxyl-terminal hydrophobic motif at Ser473 by the serine/threonine kinase mammalian target of rapamycin complex 2 (mTORC2), within a rapamycin-insensitive protein complex (27).”
From Mislocalization of the Cell Polarity Protein Scribble Promotes Mammary Tumorigenesis and Is Associated with Basal Breast Cancer (2014) · cites this paper as [27]
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Kim, D., Sarbassov, D. D., Ali, S. M., King, J. E., Latek, R. R., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2002) · Cell · doi:10.1016/s0092-8674(02)00808-5 · Cited by 3,051
Self-citationMechanism of activation of protein kinase B by insulin and IGF‐1.
Alessi, D. R., Andjelković, M., Caudwell, B., Cron, P. D., MORRICE, N. A., Cohen, P., & Hemmings, B. A. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb01045.x · Cited by 3,014
Alessi, D. R., James, S. R., Downes, C. P., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 2,874
Sarbassov, D. D., Ali, S. M., Kim, D.-H., Guertin, D. A., Latek, R. R., Erdjument-Bromage, H., Tempst, P., & Sabatini, D. M. (2004) · Current Biology · doi:10.1016/j.cub.2004.06.054 · Cited by 2,665
Self-citationLoewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J. L., Bonenfant, D., Oppliger, W., Jenoe, P., & Hall, M. N. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00636-6 · Cited by 1,886
Cho, H., Mu, J., Kim, J. K., Thorvaldsen, J. L., Chu, Q., Crenshaw, E. B., Kaestner, K. H., Bartolomei, M. S., Shulman, G. I., & Birnbaum, M. J. (2001) · Science · doi:10.1126/science.292.5522.1728 · Cited by 1,860
Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action
Hara, K., Maruki, Y., Long, X., Yoshino, K.-I., Oshiro, N., Sujuti, H., Tokunaga, C., Avruch, J., & Yonezawa, K. (2002) · Cell · doi:10.1016/s0092-8674(02)00833-4 · Cited by 1,810
RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1
Burnett, P. E., Barrow, R. K., Cohen, N. A., Snyder, S. H., & Sabatini, D. M. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.4.1432 · Cited by 1,130
Self-citationThe TSC1-2 tumor suppressor controls insulin–PI3K signaling via regulation of IRS proteins
Harrington, L. S., Findlay, G. M., Gray, A., Толкачева, Т. А., Wigfield, S., Rebholz, H., Barnett, J., Leslie, N. R., Cheng, S., Shepherd, P. R., et al. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200403069 · Cited by 1,123
Stephens, L., Anderson, K. E., Stokoe, D., Erdjument‐Bromage, H., Painter, G. F., Holmes, A. B., Gaffney, P. R. J., Reese, C. B., McCormick, F. P., Tempst, P., et al. (1998) · Science · doi:10.1126/science.279.5351.710 · Cited by 1,061
Kim, D., Sarbassov, D. D., Ali, S. M., Latek, R. R., Guntur, K., Erdjument‐Bromage, H., Tempst, P., & Sabatini, D. M. (2003) · Molecular Cell · doi:10.1016/s1097-2765(03)00114-x · Cited by 992
Self-citationCho, H., Thorvaldsen, J. L., Chu, Q., Feng, F., & Birnbaum, M. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100462200 · Cited by 959
Growth retardation and increased apoptosis in mice with homozygous disruption of the akt1 genePreprint
Chen, W. S., Xu, P.-Z., Gottlob, K., Chen, M.-L., Sokol, K. A., Shiyanova, T., Roninson, I. B., Weng, W., Suzuki, R., Tobe, K., et al. (2001) · Genes & Development · doi:10.1101/gad.913901 · Cited by 941
Direct control of the Forkhead transcription factor AFX by protein kinase B
Kops, G. J. P. L., Ruiter, N. D. D., De Vries-Smits, A. M. M., Powell, D. R., Bos, J. L., & Burgering, B. M. T. (1999) · Nature · doi:10.1038/19328 · Cited by 882
Amino Acid and Insulin Signaling via the mTOR/p70 S6 Kinase Pathway
Tremblay, F., & Marette, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m106703200 · Cited by 547
Akt/Protein Kinase B Is Regulated by Autophosphorylation at the Hypothetical PDK-2 Site
Toker, A., & Newton, A. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.12.8271 · Cited by 522
Regulation of Protein Kinase B/Akt-Serine 473 Phosphorylation by Integrin-linked Kinase
Persad, S., Attwell, S., Gray, V., Mawji, N. M., Deng, J. T., Leung, D., Yan, J., Sanghera, J. S., Walsh, M. P., & Dedhar, S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102940200 · Cited by 497
Identification of a PKB/Akt Hydrophobic Motif Ser-473 Kinase as DNA-dependent Protein Kinase
Feng, J., Park, J., Cron, P. D., Heß, D., & Hemmings, B. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406731200 · Cited by 488
Williams, M. R., Arthur, J. S. C., Balendran, A., KAAY, J. V. D., Poli, V., Cohen, P., & Alessi, D. R. (2000) · Current Biology · doi:10.1016/s0960-9822(00)00441-3 · Cited by 479
Balendran, A., Casamayor, A., Deák, M., Paterson, A., Gaffney, P. R. J., Currie, R. A., Downes, C. P., & Alessi, D. R. (1999) · Current Biology · doi:10.1016/s0960-9822(99)80186-9 · Cited by 434
Molecular Mechanism for the Regulation of Protein Kinase B/Akt by Hydrophobic Motif Phosphorylation
Yang, J., Cron, P. D., Thompson, V., Good, V. M., Heß, D., Hemmings, B. A., & Barford, D. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00550-6 · Cited by 418
The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB
Biondi, R. M., Kieloch, A., Currie, R. A., Deak, M., & Alessi, D. R. (2001) · The EMBO Journal · doi:10.1093/emboj/20.16.4380 · Cited by 377
Multiple Phosphoinositide 3-Kinase-Dependent Steps in Activation of Protein Kinase B
Scheid, M. P., Marignani, P. A., & Woodgett, J. R. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.17.6247-6260.2002 · Cited by 328
Taccioli, G. E., Amatucci, A. G., Beamish, H., Gell, D. A., Xiang, X. H., Torres‐Arzayus, M. I., Priestley, A., Jackson, S. P., Marshak‐Rothstein, A., Jeggo, P. A., et al. (1998) · Immunity · doi:10.1016/s1074-7613(00)80618-4 · Cited by 325
Lynch, D. K., Ellis, C. A., Edwards, P. A., & Hiles, I. D. (1999) · Oncogene · doi:10.1038/sj.onc.1203258 · Cited by 216
Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signalingPreprint
Radimerski, T., Montagne, J., Hemmings-Mieszczak, M., & Thomas, G. (2002) · Genes & Development · doi:10.1101/gad.239102 · Cited by 186
Hill, M. M. C., Andjelković, M., Brazil, D. P., Ferrari, S. M., Fabbro, D., & Hemmings, B. A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.c100174200 · Cited by 139
Identification of DNA-PK in the arthropods
Dore, A. S., Drake, A. C. B., Brewerton, S. C., & Blundell, T. L. (2003) · DNA repair · doi:10.1016/j.dnarep.2003.09.003 · Cited by 27
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Research works printed but not linked: 1
- A. L. Edinger, C. M. Linardic, G. G. Chiang, C. B. Thompson, R. T. Abraham, Cancer Res.63, 8451 (2003).
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Laplante, M., & Sabatini, D. M. (2012) · Cell · doi:10.1016/j.cell.2012.03.017 · Cited by 8,509
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Saxton, R. A., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.02.004 · Cited by 7,555
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Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
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Zoncu, R., Efeyan, A., & Sabatini, D. M. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3025 · Cited by 3,941
Self-citationAKT/PKB Signaling: Navigating the Network
Manning, B. D., & Toker, A. (2017) · Cell · doi:10.1016/j.cell.2017.04.001 · Cited by 3,772
Metadata
- Authors
- Sarbassov, D. D., Guertin, D. A., Ali, S. M., & Sabatini, D. M.
- Affiliations
- Broad Institute (US)
- Corresponding author
- Guertin, David A.
- Ali, Siraj M.
- Sabatini, David M.
- Venue
- Science
- Published
- 2005-02-18
- Volume
- 307
- Issue
- 5712
- Pages
- 1098-1101
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4238567307
- Cited by
- 6,216
- References
- 28
- Citations by year
- 2026: 119 · 2025: 176 · 2024: 229 · 2023: 275 · 2022: 254 · 2021: 323 · 2020: 324 · 2019: 318 · 2018: 350 · 2017: 329 · 2016: 303 · 2015: 396 · 2014: 358 · 2013: 386 · 2012: 378
- FWCI
- 86.71
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (R01 AI47389, R01AI047389)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Akt/protein kinase B, Rictor, mTOR, TOR signaling, Ser473 phosphorylation, PDPK1, kinase regulation, PTEN, cancer, therapeutic target, Drosophila
- MeSH terms
- Regulatory-Associated Protein of mTOR, Rapamycin-Insensitive Companion of mTOR Protein, Animals, Carrier Proteins, Cell Line, Drosophila melanogaster, Enzyme Activation, Humans, Phosphorylation, Protein Kinases, Proteins, Proto-Oncogene Proteins, Serine, Protein Serine-Threonine Kinases, Phosphatidylinositol 3-Kinases, Drosophila Proteins, RNA Interference, Cell Line, Tumor, Immunoprecipitation, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Hydrophobic and Hydrophilic Interactions, TOR Serine-Threonine Kinases, 3-Phosphoinositide-Dependent Protein Kinases
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