Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
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Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.
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AKT is a critical mediator of neuronal survival.
“which is a critical mediator of neuronal survival (Datta et al., 1997; Dudek et al., 1997).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Datta et al., 1997
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Cites
Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis
Xia, Z., Dickens, M., Raingeaud, J., Davis, R. J., & Greenberg, M. E. (1995) · Science · doi:10.1126/science.270.5240.1326 · Cited by 5,290 · see citing works
Self-citationInhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Cross, D. A. E., Alessi, D. R., Cohen, P., Andjelkovich, M., & Hemmings, B. A. (1995) · Nature · doi:10.1038/378785a0 · Cited by 5,244 · see citing works
Alessi, D., James, S., Downes, C., Holmes, A. B., Gaffney, P., Reese, C., & Cohen, P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00122-9 · Cited by 3,047 · see citing works
Mechanism 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 2,985 · see citing works
Zha, J., Harada, H., Yang, E., Jockel, J., & Korsmeyer, S. J. (1996) · Cell · doi:10.1016/s0092-8674(00)81382-3 · Cited by 2,578 · see citing works
Mechanisms and Genes of Cellular Suicide
Steller, H. (1995) · Science · doi:10.1126/science.7878463 · Cited by 2,465 · see citing works
Regulation of neuronal survival by the serine-threonine protein kinase Akt
Dudek, H., Datta, S. R., Franke, T. F., Birnbaum, M. J., Yao, R., Cooper, G. M., Segal, R. A., Kaplan, D. R., & Greenberg, M. E. (1997) · Science · doi:10.1126/science.275.5300.661 · Cited by 2,436 · see citing works
Self-citationProtein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction
Burgering, B. M. T., & Coffer, P. J. (1995) · Nature · doi:10.1038/376599a0 · Cited by 2,113 · see citing works
Bad, a heterodimeric partner for Bcl-xL and Bcl-2, displaces bax and promotes cell death
Yang, E., Zha, J., Jockel, J., Boise, L., Thompson, C. B., & Korsmeyer, S. J. (1995) · Cell · doi:10.1016/0092-8674(95)90411-5 · Cited by 2,101 · see citing works
Franke, T. F., Yang, S., Chan, T. O., Datta, K., Kazlauskas, A., Morrison, D. K., Kaplan, D. R., & Tsichlis, P. N. (1995) · Cell · doi:10.1016/0092-8674(95)90534-0 · Cited by 2,006 · see citing works
Phosphatidylinositol-3-OH kinase direct target of Ras
Rodriguez-Viciana, P., Warne, P. H., Dhand, R., Vanhaesebroeck, B., Gout, I., Fry, M. J., Waterfield, M. D., & Downward, J. (1994) · Nature · doi:10.1038/370527a0 · Cited by 1,954 · see citing works
Direct Regulation of the Akt Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate
Franke, T. F., Kaplan, D., Cantley, L., & Toker, A. (1997) · Science · doi:10.1126/science.275.5300.665 · Cited by 1,609 · see citing works
Double identity for proteins of the Bcl-2 family
Reed, J. C. (1997) · Nature · doi:10.1038/42867 · Cited by 1,494 · see citing works
Requirement for Phosphatidylinositol-3 Kinase in the Prevention of Apoptosis by Nerve Growth Factor
Yao, R., & Cooper, G. M. (1995) · Science · doi:10.1126/science.7701324 · Cited by 1,390 · see citing works
Kohn, A. D., Summers, S. A., Birnbaum, M. J., & Roth, R. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.49.31372 · Cited by 1,284 · see citing works
Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB
Kauffmann-Zeh, A., Rodriguez‐Viciana, P., Ulrich, E., Gilbert, C. S., Coffer, P. J., Downward, J., & Evan, G. I. (1997) · Nature · doi:10.1038/385544a0 · Cited by 1,148 · see citing works
The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal.Preprint
Kennedy, S. G., Wagner, A. J., Conzen, S. D., Jordán, J., Bellacosa, A., Tsichlis, P. N., & Hay, N. (1997) · Genes & Development · doi:10.1101/gad.11.6.701 · Cited by 1,074 · see citing works
Khwaja, A., Rodriguez‐Viciana, P., Wennström, S., Warne, P. H., & Downward, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.10.2783 · Cited by 1,039 · see citing works
Kulik, G., Klippel, A., & Weber, M. J. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1595 · Cited by 1,033 · see citing works
Intracellular Signaling Pathways Activated by Neuropathic Factors
Segal, R. A., & Greenberg, M. E. (1996) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.19.030196.002335 · Cited by 955 · see citing works
Self-citationA Retroviral Oncogene, akt , Encoding a Serine-Threonine Kinase Containing an SH2-Like Region
Bellacosa, A., Testa, J. R., Staal, S. P., & Tsichlis, P. N. (1991) · Science · doi:10.1126/science.1833819 · Cited by 939 · see citing works
D'Mello, S. R., Galli, C., Ciotti, T., & Calissano, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.10989 · Cited by 892 · see citing works
Meyer‐Franke, A., Kaplan, M. R., Pfrieger, F. W., & Barres, B. A. (1995) · Neuron · doi:10.1016/0896-6273(95)90172-8 · Cited by 852 · see citing works
Stewart, C. E., & Rotwein, P. S. (1996) · Physiological Reviews · doi:10.1152/physrev.1996.76.4.1005 · Cited by 785 · see citing works
Bcl-2 Targets the Protein Kinase Raf-1 to Mitochondria
Wang, H., Rapp, U. R., & Reed, J. C. (1996) · Cell · doi:10.1016/s0092-8674(00)81383-5 · Cited by 781 · see citing works
BAX Is Required for Neuronal Death after Trophic Factor Deprivation and during Development
Deckwerth, T. L., Elliott, J. L., Knudson, C. M., Johnson, E. M., Snider, W. D., & Korsmeyer, S. J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80173-7 · Cited by 749 · see citing works
Multiple extracellular signals are required for long-term oligodendrocyte survival
Barres, B. A., Schmid, R., Sendnter, M., & Raff, M. C. (1993) · Development · doi:10.1242/dev.118.1.283 · Cited by 712 · see citing works
Alessi, D. R., Barry Caudwell, F., Andjelkovic, M., Hemmings, B. A., & Cohen, P. (1996) · FEBS Letters · doi:10.1016/s0014-5793(96)01370-1 · Cited by 628 · see citing works
BCL-2 GENE FAMILY IN THE NERVOUS SYSTEM
Merry, D. E., & Korsmeyer, S. J. (1997) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.20.1.245 · Cited by 594 · see citing works
Activation of phosphoinositide 3‐kinase by interaction with Ras and by point mutation.
Rodriguez‐Viciana, P., Warne, P. H., Vanhaesebroeck, B., Waterfield, M. D., & Downward, J. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00602.x · Cited by 565 · see citing works
Carpenter, C. L., & Cantley, L. C. (1996) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(96)80060-3 · Cited by 547 · see citing works
Jones, P. F., Jakubowicz, T., Pitossi, F. J., Maurer, F., & Hemmings, B. A. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.10.4171 · Cited by 532 · see citing works
Transduction of interleukin-2 antiapoptotic and proliferative signals via Akt protein kinase
Ahmed, N. N., Grimes, H. L., Bellacosa, A., Chan, T. O., & Tsichlis, P. N. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3627 · Cited by 519 · see citing works
Coffer, P. J., & Woodgett, J. R. (1991) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1991.tb16305.x · Cited by 493 · see citing works
Klippel, A., Kavanaugh, W. M., Pot, D., & Williams, L. T. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.1.338 · Cited by 479 · see citing works
Akt, a Pleckstrin Homology Domain Containing Kinase, Is Activated Primarily by Phosphorylation
Kohn, A. D., Takeuchi, F., & Roth, R. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.36.21920 · Cited by 476 · see citing works
Galli, C., Meucci, O., Scorziello, A., Werge, T., Calissano, P., & Schettini, G. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-02-01172.1995 · Cited by 400 · see citing works
Programmed cell death in Caenorhabditis elegans
Hengartner, M. O., & Horvitz, H. R. (1994) · Current Opinion in Genetics & Development · doi:10.1016/0959-437x(94)90076-f · Cited by 378 · see citing works
Apoptosis Meets Signal Transduction: Elimination of a BAD Influence
Gajewski, T. F., & Thompson, C. B. (1996) · Cell · doi:10.1016/s0092-8674(00)81377-x · Cited by 350 · see citing works
Chinnaiyan, A. M., & Dixit, V. M. (1996) · Current Biology · doi:10.1016/s0960-9822(02)00541-9 · Cited by 349 · see citing works
Rukenstein, A., Rydel, R. E., & Greene, L. (1991) · Journal of Neuroscience · doi:10.1523/jneurosci.11-08-02552.1991 · Cited by 337 · see citing works
The activation of phosphatidylinositol 3-kinase by Ras
Kodaki, T., Woscholski, R., Hallberg, B., Rodriguez-Viciana Julian Downward, P., & Parker, P. J. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00177-9 · Cited by 329 · see citing works
D’Mello, S. R., Borodezt, K., & Soltoff, S. P. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-05-01548.1997 · Cited by 286 · see citing works
Akt Is a Direct Target of the Phosphatidylinositol 3-Kinase
Datta, K., Bellacosa, A., Chan, T. O., & Tsichlis, P. N. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.48.30835 · Cited by 279 · see citing works
Metabolic and Genetic Analyses of Apoptosis in Potassium/Serum-Deprived Rat Cerebellar Granule Cells
Miller, T. M., & Johnson Jr., E. M. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-23-07487.1996 · Cited by 228 · see citing works
Deshmukh, M., Vasilakos, J. P., Deckwerth, T. L., Lampe, P. A., Shivers, B. D., & Johnson, E. M. (1996) · The Journal of Cell Biology · doi:10.1083/jcb.135.5.1341 · Cited by 221 · see citing works
14-3-3: Modulators of Signaling Proteins?
Morrison, D. K. (1994) · Science · doi:10.1126/science.7939645 · Cited by 208 · see citing works
Bcl-2 and Bcl-2-Related Proteins in Apoptosis Regulation
Boise, L., GOTTSCHALK, A. R., Quintáns, J., & Thompson, C. B. (1995) · Current topics in microbiology and immunology · doi:10.1007/978-3-642-79437-7_8 · Cited by 203 · see citing works
Konishi, H., Kuroda, S., Tanaka, M., Matsuzaki, H., Ono, Y., Kameyama, K., Haga, T., & Kikkawa, U. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2654 · Cited by 192 · see citing works
Molecular cloning of a second form of rac protein kinase.
Jones, P. F., Jakubowicz, T., & Hemmings, B. A. (1991) · Cell Regulation · doi:10.1091/mbc.2.12.1001 · Cited by 187 · see citing works
Didichenko, S. A., Tilton, B., Hemmings, B. A., Ballmer‐Hofer, K., & Thelen, M. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70713-6 · Cited by 131 · see citing works
Oligodendrocytes and their precursors require phosphatidylinositol 3-kinase signaling for survival
Vemuri, G. S., & McMorris, F. A. (1996) · Development · doi:10.1242/dev.122.8.2529 · Cited by 128 · see citing works
Yao, R., & Gm, C. (1996) · PubMed · Cited by 120 · see citing works
Scheid, M. P., Lauener, R. W., & Duronio, V. (1995) · Biochemical Journal · doi:10.1042/bj3120159 · Cited by 112 · see citing works
Hack, N., Hidaka, H., Wakefield, M. J., & Balázs, R. (1993) · Neuroscience · doi:10.1016/0306-4522(93)90108-r · Cited by 103 · see citing works
14-3-3 Proteins: Hot numbers in signal transduction
Burbelo, P. D., & Hall, A. K. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00022-4 · Cited by 79 · see citing works
Ataliotis, P., & Mercola, M. A. (1997) · International review of cytology · doi:10.1016/s0074-7696(08)62359-1 · Cited by 78 · see citing works
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Manning, B. D., & Cantley, L. C. (2007) · Cell · doi:10.1016/j.cell.2007.06.009 · Cited by 6,115 · see citing works
Neurotrophins: Roles in Neuronal Development and Function
Huang, E. J., & Reichardt, L. F. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.677 · Cited by 4,394 · see citing works
Cellular survival: a play in three Akts
Datta, S. R., Brunet, A., & Greenberg, M. E. (1999) · Genes & Development · doi:10.1101/gad.13.22.2905 · Cited by 4,216 · see citing works
Self-citationGiancotti, F. G., & Ruoslahti, E. (1999) · Science · doi:10.1126/science.285.5430.1028 · Cited by 3,869 · see citing works
Trk Receptors: Roles in Neuronal Signal Transduction
Huang, E. J., & Reichardt, L. F. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161629 · Cited by 2,537 · see citing works
Flavonoids: antioxidants or signalling molecules?
Williams, R. J., Spencer, J. P. E., & Rice-Evans, C. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.01.001 · Cited by 2,016 · see citing works
Ras, PI(3)K and mTOR signalling controls tumour cell growth
Shaw, R. J., & Cantley, L. C. (2006) · Nature · doi:10.1038/nature04869 · Cited by 2,019 · see citing works
Neurotrophin signal transduction in the nervous system
Kaplan, D. R., & Miller, F. D. (2000) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00092-1 · Cited by 1,944 · see citing works
RAS oncogenes: weaving a tumorigenic web
Pylayeva-Gupta, Y., Grabocka, E., & Bar-Sagi, D. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3106 · Cited by 1,789 · see citing works
Steen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703 · see citing works
The yin and yang of neurotrophin action
Lu, B., Pang, P. T., & Woo, N. H. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1726 · Cited by 1,356 · see citing works
Nerve Growth Factor Signaling, Neuroprotection, and Neural Repair
Sofroniew, M. V., Howe, C. L., & Mobley, W. C. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1217 · Cited by 1,284 · see citing works
DNA damage and the balance between survival and death in cancer biology
Roos, W. P., Thomas, A. D., & Kaina, B. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.2 · Cited by 1,189 · see citing works
Mayo, L. D., & Donner, D. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181181198 · Cited by 1,230 · see citing works
Greenhough, A., Smartt, H. J. M., Moore, A. E., Roberts, H. R., Williams, A. C., Paraskeva, C., & Kaidi, A. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp014 · Cited by 1,220 · see citing works
Anoikis molecular pathways and its role in cancer progression
Paoli, P., Giannoni, E., & Chiarugi, P. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.06.026 · Cited by 1,160 · see citing works
Ten years of protein kinase B signalling: a hard Akt to follow
Brazil, D. P., & Hemmings, B. A. (2001) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(01)01958-2 · Cited by 1,177 · see citing works
Heras-Sandoval, D., Pérez-Rojas, J. M., Hernández-Damián, J., & Pedraza-Chaverri, J. (2014) · Cellular Signalling · doi:10.1016/j.cellsig.2014.08.019 · Cited by 1,091 · see citing works
Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling
SHEPHERD, P. R., WITHERS, D. J., & SIDDLE, K. (1998) · Biochemical Journal · doi:10.1042/bj3330471 · Cited by 953 · see citing works
Mutant PIK3CA promotes cell growth and invasion of human cancer cells.
Samuels, Y., Diaz, L. A., Schmidt-Kittler, O., Cummins, J. M., DeLong, L., Cheong, I., Rago, C., Huso, D. L., Lengauer, C., Kinzler, K. W., et al. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.05.014 · Cited by 915 · see citing works
Maurer, U., Charvet, C., Wagman, A. S., Dejardin, E., & Green, D. R. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.02.009 · Cited by 881 · see citing works
Molecular mechanisms of ROS production and oxidative stress in diabetes
Newsholme, P., Cruzat, V. F., Keane, K. N., Carlessi, R., & de Bittencourt, P. I. H. (2016) · Biochemical Journal · doi:10.1042/bcj20160503c · Cited by 878 · see citing works
DNA damage-induced cell death: From specific DNA lesions to the DNA damage response and apoptosis
Roos, W. P., & Kaina, B. (2013) · Cancer Letters · doi:10.1016/j.canlet.2012.01.007 · Cited by 879 · see citing works
Basu, S., Totty, N. F., Irwin, M. S., Sudol, M., & Downward, J. (2003) · Molecular Cell · doi:10.1016/s1097-2765(02)00776-1 · Cited by 843 · see citing works
Loss of <i>PTEN</i> facilitates HIF-1-mediated gene expression
Zundel, W., Schindler, C., Haas-Kogan, D., Koong, A., Kaper, F., Chen, E., Gottschalk, A. R., Ryan, H. E., Johnson, R. S., Jefferson, A. B., et al. (2000) · Genes & Development · doi:10.1101/gad.14.4.391 · Cited by 840 · see citing works
Development and Functional Diversification of Cortical Interneurons
Lim, L., Mi, D., Llorca, A., & Marín, O. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.009 · Cited by 714 · see citing works
RAS Interaction with PI3K: More Than Just Another Effector Pathway
Castellano, E., & Downward, J. (2011) · Genes & Cancer · doi:10.1177/1947601911408079 · Cited by 762 · see citing works
Neurotrophin Signaling Through the P75 Neurotrophin Receptor
Roux, P. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00016-3 · Cited by 717 · see citing works
FKBP51 Affects Cancer Cell Response to Chemotherapy by Negatively Regulating Akt
Pei, H., Li, L., Fridley, B. L., Jenkins, G. D., Kalari, K. R., Lingle, W., Petersen, G., Lou, Z., & Wang, L. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.07.016 · Cited by 709 · see citing works
Drug-induced oxidative stress and toxicity
Deavall, D. G., Martin, E. A., Horner, J. M., & Roberts, R. (2012) · Journal of Toxicology · doi:10.1155/2012/645460 · Cited by 689 · see citing works
Newsholme, P., Haber, E. P., Hirabara, S. M., Rebelato, E. L. O., Procopio, J., Morgan, D., Oliveira‐Emilio, H. C., Carpinelli, A. R., & Curi, R. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.135871 · Cited by 684 · see citing works
The PI3K/AKT/mTOR interactive pathway
Ersahin, T., Tuncbag, N., & Cetin-Atalay, R. (2015) · Molecular BioSystems · doi:10.1039/c5mb00101c · Cited by 683 · see citing works
Kim, I., Kim, H. G., So, J.-N., Kim, J. H., Kwak, H. J., & Koh, G. Y. (2000) · Circulation Research · doi:10.1161/01.res.86.1.24 · Cited by 649 · see citing works
Is Alzheimer’s disease a type 3 diabetes? A critical appraisal
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Akt Enhances Mdm2-mediated Ubiquitination and Degradation of p53
Ogawara, Y., Kishishita, S., Obata, T., Isazawa, Y., Suzuki, T., Tanaka, K., Masuyama, N., & Gotoh, Y. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109745200 · Cited by 617 · see citing works
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Hata, A. N., Engelman, J. A., & Faber, A. C. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0011 · Cited by 619 · see citing works
Brognard, J., Sierecki, E., Gao, T., & Newton, A. C. (2007) · Molecular Cell · doi:10.1016/j.molcel.2007.02.017 · Cited by 591 · see citing works
Chong, Z. Z., Li, F., & Maiese, K. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.02.004 · Cited by 536 · see citing works
Li, Y. C., Park, M. J., Ye, S.-K., Kim, C.-W., & Kim, Y.-N. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.050959 · Cited by 536 · see citing works
Signaling pathways involved in colorectal cancer: pathogenesis and targeted therapy
Li, Q., Geng, S., Luo, H., Wang, W., Mo, Y.-Q., Luo, Q., Wang, L., Song, G.-B., Sheng, J.-P., & Xu, B. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01953-7 · Cited by 546 · see citing works
Lee, J. Y., Ye, J., Gao, Z., Youn, H. S., Lee, W. H., Zhao, L., Sizemore, N., & Hwang, D. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305213200 · Cited by 524 · see citing works
A motif-based profile scanning approach for genome-wide prediction of signaling pathways
Yaffe, M. B., Leparc, G. G., Lai, J., Obata, T., Volinia, S., & Cantley, L. C. (2001) · Nature Biotechnology · doi:10.1038/86737 · Cited by 517 · see citing works
Tumour cell survival signalling by the ERK1/2 pathway
Balmanno, K., & Cook, S. J. (2009) · Cell Death & Differentiation · doi:10.1038/cdd.2008.148 · Cited by 484 · see citing works
mTOR Kinase Inhibition Causes Feedback-Dependent Biphasic Regulation of AKT Signaling
Rodrik-Outmezguine, V. S., Chandarlapaty, S., Pagano, N. C., Poulikakos, P. I., Scaltriti, M., Moskatel, E., Baselga, J., Guichard, S., & Rosen, N. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-11-0085 · Cited by 442 · see citing works
Novel functions of TIMPs in cell signaling
Chirco, R., Liu, X.-W., Jung, K.-K., & Kim, H.-R. C. (2006) · Cancer and Metastasis Reviews · doi:10.1007/s10555-006-7893-x · Cited by 401 · see citing works
Akt suppresses androgen-induced apoptosis by phosphorylating and inhibiting androgen receptor.
Lin, H.-K., Yeh, S., Kang, H.-Y., & Chang, C. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.121173298 · Cited by 401 · see citing works
The role of mitochondria in protection of the heart by preconditioning
Halestrap, A. P., Clarke, S. J., & Khaliulin, I. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.05.008 · Cited by 390 · see citing works
Expression of CX <sub>3</sub> CR1 chemokine receptors on neurons and their role in neuronal survival
Meucci, O., Fatatis, A., Simen, A. A., & Miller, R. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.090017497 · Cited by 385 · see citing works
The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes
Berwick, D. C., Hers, I., Heesom, K. J., Moule, S. K., & Tavareá, J. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204681200 · Cited by 383 · see citing works
The role of the mitochondrial permeability transition pore in heart disease
Halestrap, A. P., & Pasdois, P. (2009) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.12.017 · Cited by 362 · see citing works
Wang, J.-M., Chao, J.-R., Chen, W., Kuo, M.-L., Yen, J. J.-Y., & Yang-Yen, H.-F. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.9.6195 · Cited by 357 · see citing works
PTEN Protects p53 from Mdm2 and Sensitizes Cancer Cells to Chemotherapy
Mayo, L. D., Dixon, J. E., Durden, D. L., Tonks, N. K., & Donner, D. B. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m108302200 · Cited by 351 · see citing works
Coordination and communication between the p53 and IGF-1–AKT–TOR signal transduction pathways
Levine, A. J., Feng, Z., Mak, T. W., You, H., & Jin, S. (2006) · Genes & Development · doi:10.1101/gad.1363206 · Cited by 321 · see citing works
Diabetes and apoptosis: lipotoxicity
Kusminski, C. M., Shetty, S., Orci, L., Unger, R. H., & Scherer, P. E. (2009) · Apoptosis · doi:10.1007/s10495-009-0352-8 · Cited by 302 · see citing works
Sun, C., Hobor, S., Bertotti, A., Zecchin, D., Huang, S., Galimi, F., Cottino, F., Prahallad, A., Grernrum, W., Tzani, A., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.02.045 · Cited by 304 · see citing works
Zhao, C., Yasumura, D., Li, X., Matthes, M., Lloyd, M., Nielsen, G., Ahern, K., Snyder, M., Bok, D., Dunaief, J. L., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci44303 · Cited by 303 · see citing works
Pyramidal cell regulation of interneuron survival sculpts cortical networks
Wong, F. K., Bercsenyi, K., Sreenivasan, V., Portalés, A., Fernández-Otero, M., & Marín, O. (2018) · Nature · doi:10.1038/s41586-018-0139-6 · Cited by 286 · see citing works
Derksen, P. W. B., Keehnen, R. M. J., Evers, L. M., van Oers, M. H. J., Spaargaren, M., & Pals, S. T. (2002) · Blood · doi:10.1182/blood.v99.4.1405 · Cited by 274 · see citing works
Obesity and cancer: existing and new hypotheses for a causal connection
Stone, T. W., McPherson, M., & Gail Darlington, L. (2018) · eBioMedicine · doi:10.1016/j.ebiom.2018.02.022 · Cited by 262 · see citing works
Kadekaro, A. L., Kavanagh, R., Kanto, H., Terzieva, S., Hauser, J., Kobayashi, N., Schwemberger, S., Cornelius, J., Babcock, G., Shertzer, H. G., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-4535 · Cited by 259 · see citing works
Yamaguchi, A., Tamatani, M., Matsuzaki, H., Namikawa, K., Kiyama, H., Vitek, M. P., Mitsuda, N., & Tohyama, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008552200 · Cited by 242 · see citing works
Macdonald, A., Campbell, D. G., Toth, R., McLauchlan, H., Hastie, C. J., & Arthur, J. S. C. (2006) · BMC Cell Biology · doi:10.1186/1471-2121-7-1 · Cited by 246 · see citing works
Apoptosis of Retinal Ganglion Cells in Glaucoma
Nickells, R. W. (1999) · Survey of Ophthalmology · doi:10.1016/s0039-6257(99)00029-6 · Cited by 232 · see citing works
Malagelada, C., Jin, Z. H., & Greene, L. A. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3928-08.2008 · Cited by 228 · see citing works
Stiles, B., Groszer, M., Wang, S., Jiao, J., & Wu, H. (2004) · Developmental Biology · doi:10.1016/j.ydbio.2004.06.008 · Cited by 230 · see citing works
Regulation of Proliferation, Differentiation and Survival by the IL-3/IL-5/GM-CSF Receptor Family
de Groot, R. P., Coffer, P. J., & Koenderman, L. (1998) · Cellular Signalling · doi:10.1016/s0898-6568(98)00023-0 · Cited by 215 · see citing works
Suliman, H. B., Carraway, M. S., Welty-Wolf, K. E., Whorton, A. R., & Piantadosi, C. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m304719200 · Cited by 189 · see citing works
Duan, W., Lee, J., Guo, Z., & Mattson, M. P. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:16:1:1 · Cited by 183 · see citing works
ERK1/2‐dependent phosphorylation of BimEL promotes its rapid dissociation from Mcl‐1 and Bcl‐xL
Ewings, K. E., Hadfield‐Moorhouse, K., Wiggins, C. M., Wickenden, J. A., Balmanno, K., Gilley, R., Degenhardt, K., White, E., & Cook, S. J. (2007) · The EMBO Journal · doi:10.1038/sj.emboj.7601723 · Cited by 176 · see citing works
Macrophage LRP-1 Controls Plaque Cellularity by Regulating Efferocytosis and Akt Activation
Yancey, P. G., Blakemore, J., Ding, L., Fan, D., Overton, C. D., Zhang, Y., Linton, M. F., & Fazio, S. (2010) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.109.202051 · Cited by 168 · see citing works
López-Camarillo, C., Aréchaga Ocampo, E., López Casamichana, M., Pérez-Plasencia, C., Álvarez-Sánchez, E., & Marchat, L. A. (2011) · International Journal of Molecular Sciences · doi:10.3390/ijms13010142 · Cited by 165 · see citing works
Cohen, P. (1999) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1999.0399 · Cited by 158 · see citing works
Castro-Caldas, M., Carvalho, A. N., Rodrigues, E., Henderson, C. J., Wolf, C. R., Rodrigues, C. M. P., & Gama, M. J. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8295-4 · Cited by 156 · see citing works
Filipović, D., Todorović, N., Bernardi, R. E., & Gass, P. (2017) · Brain Structure and Function · doi:10.1007/s00429-016-1218-9 · Cited by 138 · see citing works
Jang, S.-W., Yang, S.-J., Srinivasan, S., & Ye, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m704542200 · Cited by 133 · see citing works
MAST1 drives cisplatin resistance in human cancers by rewiring cRaf-independent MEK activation
Jin, L., Chun, J., Pan, C., Li, D., Lin, R., Alesi, G. N., Wang, X., Kang, H.-B., Song, L., Wang, D., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.06.012 · Cited by 132 · see citing works
Blanquie, O., Yang, J.-W., Kilb, W., Sharopov, S., Sinning, A., & Luhmann, H. J. (2017) · eLife · doi:10.7554/elife.27696 · Cited by 114 · see citing works
Role of PI3K in the generation and survival of B cells
Werner, M., Hobeika, E., & Jumaa, H. (2010) · Immunological Reviews · doi:10.1111/j.1600-065x.2010.00934.x · Cited by 122 · see citing works
Mathews, M. T., & Berk, B. C. (2008) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.156406 · Cited by 120 · see citing works
Hsp70: Anti-apoptotic and Tumorigenic Protein
Rérole, A.-L., Jego, G., & Garrido, C. (2011) · Methods in Molecular Biology · doi:10.1007/978-1-61779-295-3_16 · Cited by 118 · see citing works
Plasmalogens rescue neuronal cell death through an activation of AKT and ERK survival signaling
Hossain, M. S., Ifuku, M., Take, S., Kawamura, J., Miake, K., & Katafuchi, T. (2013) · PLoS ONE · doi:10.1371/journal.pone.0083508 · Cited by 116 · see citing works
Pengetnze, Y., Steed, M., Roby, K. F., Terranova, P. F., & Taylor, C. C. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2003.08.012 · Cited by 107 · see citing works
Lindner, A. U., Concannon, C. G., Boukes, G. J., Cannon, M. D., Llambi, F., Ryan, D., Boland, K., Kehoe, J., McNamara, D. A., Murray, F., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-2269 · Cited by 105 · see citing works
Signal-transduction cascades as targets for therapeutic intervention by natural products
Cardenas, M. E., Sanfridson, A., Cutler, N. S., & Heitman, J. (1998) · Trends in Biotechnology · doi:10.1016/s0167-7799(98)01239-6 · Cited by 101 · see citing works
Murao, K., Ohyama, T., Imachi, H., Ishida, T., Cao, W. M., Namihira, H., Sato, M., Wong, N. C. W., & Takahara, J. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3497 · Cited by 99 · see citing works
ERK1/2 Antagonizes Glycogen Synthase Kinase-3β-induced Apoptosis in Cortical Neurons
Hetman, M., Hsuan, S.-L., Habas, A., Higgins, M. J., & Xia, Z. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111227200 · Cited by 88 · see citing works
Yuan, Z., Kim, D., Shu, S., Wu, J., Guo, J., Xiao, L., Kaneko, S., Coppola, D., & Cheng, J. Q. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.059675 · Cited by 78 · see citing works
RetractedGlucocorticoid Modulation of Insulin Signaling in Human Subcutaneous Adipose Tissue
Gathercole, L. L., Bujalska, I. J., Stewart, P. M., & Tomlinson, J. W. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1399 · Cited by 73 · see citing works
Adeosun, S. O., Gordon, D. M., Weeks, M. F., Moore, K. H., Hall, J. E., Hinds, T. D., & Stec, D. E. (2018) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00495.2017 · Cited by 73 · see citing works
Girard, S.-A., Bah, T. M., Kaloustian, S., Lada-Moldovan, L., Rondeau, I., Tompkins, T. A., Godbout, R., & Rousseau, G. (2009) · British Journal of Nutrition · doi:10.1017/s0007114509990766 · Cited by 70 · see citing works
Hein, A. L., Seshacharyulu, P., Rachagani, S., Sheinin, Y. M., Ouellette, M. M., Ponnusamy, M. P., Mumby, M. C., Batra, S. K., & Yan, Y. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2119 · Cited by 66 · see citing works
Rubovitch, V., Edut, S., Sarfstein, R., Werner, H., & Pick, C. G. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.01.021 · Cited by 61 · see citing works
Rebecca, V. W., Massaro, R. R., Fedorenko, I. V., Sondak, V. K., Anderson, A. R. A., Kim, E., Amaravadi, R. K., Maria‐Engler, S. S., Messina, J. L., Gibney, G. T., et al. (2014) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12227 · Cited by 58 · see citing works
Onyango, I. G., Bennett, J. P., & Tuttle, J. B. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.01.026 · Cited by 56 · see citing works
Hwang, Y. P., Yun, H. J., Chun, H. K., Chung, Y. C., Kim, H. K., Jeong, M. H., Yoon, T. R., & Jeong, H. G. (2009) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2009.07.017 · Cited by 56 · see citing works
Pitts, T. M., Newton, T. P., Bradshaw-Pierce, E. L., Addison, R., Arcaroli, J. J., Klauck, P. J., Bagby, S. M., Hyatt, S. L., Purkey, A., Tentler, J. J., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0113037 · Cited by 54 · see citing works
Increase in CIP2A expression is associated with doxorubicin resistance
Choi, Y. A., Park, J. S., Park, M. Y., Oh, K. S., Lee, M. S., Lim, J.-S., Kim, K. I., Kim, K.-Y., Kwon, J., Yoon, D. Y., et al. (2011) · FEBS Letters · doi:10.1016/j.febslet.2011.01.018 · Cited by 54 · see citing works
Jomary, C., Cullen, J., & Jones, S. E. (2006) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.05-1176 · Cited by 51 · see citing works
Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease
Reich, N., & Hölscher, C. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.614828 · Cited by 48 · see citing works
“Furthermore, in IGF1-positive brain areas, the increased phosphorylation of Akt, enhanced levels of the apoptosis-suppressing protein Bcl-2 as well as the inactivation of the apoptosis-mediator Bad were detected (Datta et al., 1997).”
BackgroundBichet, M. C., Adderley, J., Avellaneda-Franco, L., Magnin-Bougma, I., Torriero-Smith, N., Gearing, L. J., Deffrasnes, C., David, C., Pepin, G., Gantier, M. P., et al. (2023) · PLOS Biology · doi:10.1371/journal.pbio.3002341 · Cited by 47 · see citing works
- Authors
- Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E.
- Affiliations
- Boston Children's Hospital (US)
- Emory University (US)
- Corresponding author
- Greenberg, Michael E
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-10
- Volume
- 91
- Issue
- 2
- Pages
- 231-241
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2097767970
- Cited by
- 5,689
- References
- 57
- Citations by year
- 2026: 58 · 2025: 65 · 2024: 70 · 2023: 82 · 2022: 60 · 2021: 88 · 2020: 101 · 2019: 113 · 2018: 110 · 2017: 140 · 2016: 143 · 2015: 163 · 2014: 185 · 2013: 237 · 2012: 242
- FWCI
- 80.36
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (GM 53165)
- National Institute of Neurological Disorders and Stroke (NS 28829)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD018655, P30HD-18655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- Akt phosphorylation, Bad, Bcl-2 family proteins, PI3K/Akt signaling, apoptosis, cell survival, growth factor signaling, primary neurons, site-specific phosphorylation
- MeSH terms
- Amino Acid Sequence, Animals, Carrier Proteins, Cell Survival, Insulin-Like Growth Factor I, Mice, Inbred BALB C, Molecular Sequence Data, Neurons, Phosphorylation, Proto-Oncogene Proteins, Serine, Signal Transduction, 3T3 Cells, Cell Death, Protein Serine-Threonine Kinases, bcl-Associated Death Protein, Proto-Oncogene Proteins c-akt, Mice
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