PreprintCited by 4,216Cell death mechanisms and regulationPI3K/AKT/mTOR signaling in cancerNerve injury and regeneration

The DOI matches its Crossref record; 229 of the 233 references it cites were found in a registry or an index.

Cellular survival: a play in three Akts

Open access

Datta, S. R., Brunet, A., Greenberg, M. E.·1999·Genes & Development

DOI 10.1101/gad.13.22.2905

Open this paper in CoChat — free account Open PDF

Abstract

The programmed cell death that occurs as part of normal mammalian development was first observed nearly a century ago (Collin 1906). It has since been established that approximately half of all neurons in the neuroaxis and >99.9% of the total number of cells generated during the course of a human lifetime go on to die through a process of apoptosis (for review, see Datta and Greenberg 1998; Vaux and Korsmeyer 1999). The induction of developmental cell death is a highly regulated process and can be suppressed by a variety of extracellular stimuli. The purification in the 1950s of the nerve growth factor (NGF), which promotes the survival of sympathetic neurons, set the stage for the discovery that peptide trophic factors promote the survival of a wide variety of cell types in vitro and in vivo (Levi-Montalcini 1987). The profound biological consequences of growth factor (GF) suppression of apoptosis are exemplified by the critical role of target-derived neurotrophins in the survival of neurons and the maintenance of functional neuronal circuits. (Pettmann and Henderson 1998). Recently, the ability of trophic factors to promote survival have been attributed, at least in part, to the phosphatidylinositide 38-OH kinase (PI3K)/c-Akt kinase cascade. Several targets of the PI3K/c-Akt signaling pathway have been recently identified that may underlie the ability of this regulatory cascade to promote survival. These substrates include two components of the intrinsic cell death machinery, BAD and caspase 9, transcription factors of the forkhead family, and a kinase, IKK, that regulates the NF-kB transcription factor. This article reviews the mechanisms by which survival factors regulate the PI3K/c-Akt cascade, the evidence that activation of the PI3K/c-Akt pathway promotes cell survival, and the current spectrum of c-Akt targets and their roles in mediating c-Akt-dependent cell survival.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Integrity signals

Registry

Crossref · 10.1101/gad.13.22.2905

Cites

229 of 229 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Mitochondria and Apoptosis
Green, D. R., & Reed, J. C. (1998) · Science · doi:10.1126/science.281.5381.1309 · Cited by 9,051
WAF1, a potential mediator of p53 tumor suppression
El-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W., & Vogelstein, B. (1993) · Cell · doi:10.1016/0092-8674(93)90500-p · Cited by 8,321
Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery
Datta, S. R., Dudek, H., Tao, X., Masters, S., Fu, H., Gotoh, Y., & Greenberg, M. E. (1997) · Cell · doi:10.1016/s0092-8674(00)80405-5 · Cited by 5,689
Self-citation
Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor
Brunet, A., Bonni, A., Zigmond, M. J., Lin, M. Z., Juo, P., Hu, L. S., Anderson, M. J., Arden, K. C., Blenis, J., & Greenberg, M. E. (1999) · Cell · doi:10.1016/s0092-8674(00)80595-4 · Cited by 5,594
Self-citation
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 5,273
Self-citation
Inhibition 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
The Protein Kinase Family: Conserved Features and Deduced Phylogeny of the Catalytic Domains
Hanks, S. K., Quinn, A. M., & Hunter, T. R. (1988) · Science · doi:10.1126/science.3291115 · Cited by 5,040
Apoptosis by Death Factor
Nagata, S. (1997) · Cell · doi:10.1016/s0092-8674(00)81874-7 · Cited by 4,934
PTEN , a Putative Protein Tyrosine Phosphatase Gene Mutated in Human Brain, Breast, and Prostate Cancer
Li, J., Yen, C., Liaw, D., Podsypanina, K., Bose, S., Wang, S. I., Puc, J., Miliaresis, C., Rodgers, L., McCombie, R., et al. (1997) · Science · doi:10.1126/science.275.5308.1943 · Cited by 4,785
Tumor suppressor p53 is a direct transcriptional activator of the human bax gene
Toshiyuki, M., & Reed, J. C. (1995) · Cell · doi:10.1016/0092-8674(95)90412-3 · Cited by 4,063

Show all 233 references

Research works printed but not linked: 4

Bonni, A., A. Brunet, A.E. West, S.R. Datta, and M.E. Greenberg. 1999. The ras-MAPK signaling pathway promotes cell sur- vival via a dual transcription-dependent and transcription- independent mechanism. Science (in press).
Cheng, J.Q., B. Ruggeri, W.M. Klein, G. Sonoda, D.A. Altomare, D.K. Watson, and J.R. Testa. 1996. Amplification of AKT2 in human pancreatic cancer cells and inhibition of AKT2 ex- pression and tunorigeneicity by antisense RNA. Proc. Natl. Acad. Sci. 93: 3636-3641.
Kitamura, T., W. Ogawa, H. Sakaue, Y. Hino, S. Kuroda, M. Takata, M. Matsumoto, T. Maeda, H. Konishi, U. Kikkawa et al. 1998a. Requirement for activation of the serine-threo- nine kinase Akt (PKB) in insulin stimulation of protein syn- thesis but not of glucose transport. Mol. Cell. Biol. 18: 3708- 3717.
Staal, S.P. 1987. Molecular cloning of the akt oncogene and its human homologs Akt1 and Akt2: Amplification of Akt1 in a primary human gastric adenocarcinoma. Proc. Natl. Acad. Sci. 84: 5034-5037.

Sorted by citations

Items 401–500 of 1,017

FOXO Transcription Factors in Cell-Cycle Regulation and the Response to Oxidative Stress
Furukawa‐Hibi, Y., Kobayashi, Y., Chen, C., & Motoyama, N. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.752 · Cited by 228
The Anti-apoptotic Effect of Notch-1 Requires p56 -dependent, Akt/PKB-mediated Signaling in T Cells
Sade, H., Krishna, S., & Sarin, A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m309924200 · Cited by 232
Glycogen Synthase Kinase 3β Regulates GATA4 in Cardiac Myocytes
Morisco, C., Seta, K., Hardt, S. E., Lee, Y., Vatner, S. F., & Sadoshima, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m103166200 · Cited by 230
Regulation of Bcl-xL: a little bit of this and a little bit of STAT
Grad, J. M., Zeng, X., & Boise, L. (2000) · Current Opinion in Oncology · doi:10.1097/00001622-200011000-00006 · Cited by 236
Cell metabolism in the regulation of programmed cell death
Plas, D. R., & Thompson, C. B. (2002) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(01)00528-8 · Cited by 232
Spatially and Functionally Distinct Roles of the PI3-K Effector Pathway during NGF Signaling in Sympathetic Neurons
Kuruvilla, R., Ye, H., & Ginty, D. D. (2000) · Neuron · doi:10.1016/s0896-6273(00)00061-1 · Cited by 231
Activation of PI3K/Akt pathway by PTEN reduction and PIK3CA mRNA amplification contributes to cisplatin resistance in an ovarian cancer cell line
Lee, S., Choi, E., Jin, C., & Kim, D. (2005) · Gynecologic Oncology · doi:10.1016/j.ygyno.2004.11.051 · Cited by 230
PI3K-AKT-mTOR inhibitors in breast cancers: From tumor cell signaling to clinical trials
Dey, N., De, P. K., & Leyland-Jones, B. R. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.037 · Cited by 237
Dopamine Induces a PI3-Kinase-Independent Activation of Akt in Striatal Neurons: A New Route to cAMP Response Element-Binding Protein Phosphorylation
Brami‐Cherrier, K., Valjent, E., García, M., Pagès, C., Hipskind, R. A., & Caboche, J. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08911.2002 · Cited by 230
Tauroursodeoxycholic acid protects rat hepatocytes from bile acid–induced apoptosis via activation of survival pathways
Schoemaker, M. H., de la Rosa, L. C., Buist-Homan, M., Vrenken, T. E., Havinga, R., Poelstra, K., Haisma, H. J., Jansen, P. L. M., & Moshage, H. (2004) · Hepatology · doi:10.1002/hep.20246 · Cited by 229
Myocardial AKT: The Omnipresent Nexus
Sussman, M. A., Völkers, M., Fischer, K. M., Bailey, B., Cottage, C. T., Din, S., Gude, N. A., Avitabile, D., Alvarez, R., Sundararaman, B., et al. (2011) · Physiological Reviews · doi:10.1152/physrev.00024.2010 · Cited by 237
The TORrid affairs of viruses: effects of mammalian DNA viruses on the PI3K–Akt–mTOR signalling pathway
Buchkovich, N. J., Yu, Y., Zampieri, C. A., & Alwine, J. C. (2008) · Nature Reviews Microbiology · doi:10.1038/nrmicro1855 · Cited by 238
The hepatitis C virus core protein of genotypes 3a and 1b downregulates insulin receptor substrate 1 through genotype‐specific mechanisms†
Pazienza, V., Clément, S., Pugnale, P., Conzelmann, S., Foti, M., Mangia, A., & Negro, F. (2007) · Hepatology · doi:10.1002/hep.21634 · Cited by 229
Targeting the PI3-Kinase/Akt/mTOR Signaling Pathway
Hassan, B., Akçakanat, A., Holder, A. M., & Meric‐Bernstam, F. (2013) · Surgical Oncology Clinics of North America · doi:10.1016/j.soc.2013.06.008 · Cited by 230
Anaplastic lymphoma kinase proteins in growth control and cancer
Pulford, K. A. F., Morris, S. W., & Turturro, F. (2004) · Journal of Cellular Physiology · doi:10.1002/jcp.10472 · Cited by 226
Expressionof Drosophila FOXO regulates growth and can phenocopy starvation
Kramer, J. M., Davidge, J. T., Lockyer, J. M., & Staveley, B. E. (2003) · BMC Developmental Biology · doi:10.1186/1471-213x-3-5 · Cited by 225
Lymphatic endothelium: a new frontier of metastasis research
Karkkainen, M. J., Mäkinen, T., & Alitalo, K. K. (2002) · Nature Cell Biology · doi:10.1038/ncb0102-e2 · Cited by 226
Comparative signaling pathways of insulin-like growth factor-1 and brain-derived neurotrophic factor in hippocampal neurons and the role of the PI3 kinase pathway in cell survival
Zheng, W., & Quirion, R. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02350.x · Cited by 225
The chitinase 3-like protein human cartilage glycoprotein 39 inhibits cellular responses to the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha
Ling, H., & Recklies, A. D. (2004) · Biochemical Journal · doi:10.1042/bj20040099 · Cited by 225
The role of FOXO1 in β-cell failure and type 2 diabetes mellitus
Kitamura, T. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.157 · Cited by 225
The Insulin Receptor and Its Cellular Targets1
Kido, Y., Nakae, J., & Accili, D. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.3.7306 · Cited by 228
β-Amyloid Peptide at Sublethal Concentrations Downregulates Brain-Derived Neurotrophic Factor Functions in Cultured Cortical Neurons
Tong, L., Balazs, R., Thornton, P. L., & Cotman, C. W. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5463-03.2004 · Cited by 221
Activation of the IκB Kinase Complex and Nuclear Factor-κB Contributes to Mutant Huntingtin Neurotoxicity
Khoshnan, A., Ko, J., Watkin, E. E., Paige, L. A., Reinhart, P. H., & Patterson, P. H. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2675-04.2004 · Cited by 223
Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma
Nakanishi, K., Sakamoto, M., Yamasaki, S., Todo, S., & Hirohashi, S. (2004) · Cancer · doi:10.1002/cncr.20774 · Cited by 222
Regulation of Multidrug Resistance in Cancer Cells by Hyaluronan
Misra, S., Ghatak, S., Zoltan-Jones, A., & Toole, B. P. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.c300173200 · Cited by 225
Oncogenic pathways and the electron transport chain: a dangeROS liaison
Raimondi, V., Ciccarese, F., & Ciminale, V. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0651-y · Cited by 232
Vascular Endothelial Growth Factor Up-regulates ICAM-1 Expression via the Phosphatidylinositol 3 OH-kinase/AKT/Nitric Oxide Pathway and Modulates Migration of Brain Microvascular Endothelial Cells
Radisavljevic, Z., Avraham, H. K., & Avraham, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002448200 · Cited by 224
Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor
Hayashi, H., Ichihara, M., Iwashita, T., Murakami, H., Shimono, Y., Kawai, K., Kurokawa, K., Murakumo, Y., Imai, T., Funahashi, H., et al. (2000) · Oncogene · doi:10.1038/sj.onc.1203799 · Cited by 222
OXIDIZED LOW‐DENSITY LIPOPROTEIN INDUCES ENDOTHELIAL PROGENITOR CELL SENESCENCE, LEADING TO CELLULAR DYSFUNCTION
Imanishi, T., Hano, T., Sawamura, T., & Nishio, I. (2004) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2004.04022.x · Cited by 221
PKB and the mitochondria: AKTing on apoptosis
Parcellier, A., Tintignac, L. A. J., Zhuravleva, E., & Hemmings, B. A. (2007) · Cellular Signalling · doi:10.1016/j.cellsig.2007.07.010 · Cited by 223
Dosage-Dependent Effects of Akt1/Protein Kinase Bα (PKBα) and Akt3/PKBγ on Thymus, Skin, and Cardiovascular and Nervous System Development in Mice
Yang, Z., Tschopp, O., Di‐Poï, N., Bruder, E., Baudry, A., Dummler, B. A., Wahli, W., & Hemmings, B. A. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.23.10407-10418.2005 · Cited by 219
p53 regulates cell survival by inhibiting PIK3CA in squamous cell carcinomasPreprint
Singh, B., Reddy, P. G., Goberdhan, A., Walsh, C., Dao, S., Ngai, I. M., Chou, T., O‐charoenrat, P., Levine, A. J., Rao, P. H., et al. (2002) · Genes & Development · doi:10.1101/gad.973602 · Cited by 219
The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B.
Montaner, S., Sodhi, A., Pece, S., Mesri, E. A., & Gutkind, J. S. (2001) · PubMed · Cited by 218
Astrocyte elevated gene-1 activates cell survival pathways through PI3K-Akt signaling
Lee, S.-G., Su, Z.-Z., Emdad, L., Sarkar, D., Franke, T. F., & Fisher, P. B. (2007) · Oncogene · doi:10.1038/sj.onc.1210713 · Cited by 217
The c‐myc Promoter: Still MysterY and Challenge
(2008) · Advances in Cancer Research · doi:10.1016/s0065-230x(07)99004-1 · Cited by 211
Towards a mechanistic understanding of tumor invasion—lessons from theα 6 β 4integrin
Mercurio, A. M., & Rabinovitz, I. (2001) · Seminars in Cancer Biology · doi:10.1006/scbi.2000.0364 · Cited by 215
Random walks and cell size
Agutter, P. S., & Wheatley, D. N. (2000) · BioEssays · doi:10.1002/1521-1878(200011)22:11 · Cited by 56
Luteolin Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis; Inhibition of Endothelial Cell Survival and Proliferation by Targeting Phosphatidylinositol 3′-Kinase Activity
Bagli, E., Stefaniotou, M. I., Morbidelli, L., Ziche, M., Psilas, K. G., Murphy, C., & Fotsis, T. (2004) · Cancer Research · doi:10.1158/0008-5472.can-03-3104 · Cited by 215
Akt inhibits Myt1 in the signalling pathway that leads to meiotic G2/M-phase transition
Okumura, E., Fukuhara, T., Yoshida, H., Hanada, S.-I., Kozutsumi, R., Mori, M., Tachibana, K., & Kishimoto, T. (2002) · Nature Cell Biology · doi:10.1038/ncb741 · Cited by 214
Transcriptional repression of p53 by parkin and impairment by mutations associated with autosomal recessive juvenile Parkinson's disease
da Costa, C. A., Sunyach, C., Giaime, E., West, A. B., Corti, O., Brice, A., Safe, S. H., Abou‐Sleiman, P. M., Wood, N. W., Takahashi, H., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1981 · Cited by 211
The ins and outs of signalling
Downward, J. (2001) · Nature · doi:10.1038/35081138 · Cited by 213
Nuclear Targeting of Akt Enhances Kinase Activity and Survival of Cardiomyocytes
Shiraishi, I., Melendez, J., Ahn, Y., Skavdahl, M., Murphy, E., Welch, S., Schaefer, E., Walsh, K. X., Rosenzweig, A., Torella, D., et al. (2004) · Circulation Research · doi:10.1161/01.res.0000124394.01180.be · Cited by 212
The Domains of Apoptosis: A Genomics Perspective
Reed, J. C., Doctor, K. S., & Godzik, A. (2004) · Science s STKE · doi:10.1126/stke.2392004re9 · Cited by 213
Protein Kinase B/AKT 1 Plays a Pivotal Role in Insulin-like Growth Factor-1 Receptor Signaling Induced 3T3-L1 Adipocyte Differentiation
Xu, J., & Liao, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402297200 · Cited by 213
RETRACTED: Effects of Artesunate on chondrocyte proliferation, apoptosis and autophagy through the PI3K/AKT/mTOR signaling pathway in rat models with rheumatoid arthritis
Feng, F., & Qiu, H. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.03.142 · Cited by 211
Retracted
Tauroursodeoxycholic acid reduces apoptosis and protects against neurological injury after acute hemorrhagic stroke in rats
Rodrigues, C. M. P., Solá, S., Nan, Z., Castro, R. E., Ribeiro, P. S., Low, W. C., & Steer, C. J. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031632100 · Cited by 210
Phosphatidylinositol 3‐kinase is a central mediator of NMDA receptor signalling to MAP kinase (Erk1/2), Akt/PKB and CREB in striatal neurones
Perkinton, M. S., Ip, J. E., Wood, G. L., Crossthwaite, A. J., & Williams, R. J. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00699.x · Cited by 212
Proinflammatory Cytokines Activate the Intrinsic Apoptotic Pathway in β-Cells
Grunnet, L. G., Aikin, R. A., Tonnesen, M., Paraskevas, S., Blaabjerg, L., Størling, J., Rosenberg, L. C., Billestrup, N., Maysinger, D., & Mandrup-Poulsen, T. R. (2009) · Diabetes · doi:10.2337/db08-0178 · Cited by 215
Flavonoids as Protein Kinase Inhibitors for Cancer Chemoprevention: Direct Binding and Molecular Modeling
Hou, D., & Kumamoto, T. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2816 · Cited by 216
Insulin regulates the activity of forkhead transcription factor Hnf-3β/Foxa-2 by Akt-mediated phosphorylation and nuclear/cytosolic localization
Wolfrum, C., Besser, D., Luca, E., & Stoffel, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1931483100 · Cited by 212
The epidermal growth factor receptor pathway mediates resistance to sequential administration of radiation and chemotherapy in primary human glioblastoma cells in a RAS-dependent manner.
Chakravarti, A., Chakladar, A., Delaney, M. A., Latham, D. E., & Loeffler, J. S. (2002) · PubMed · Cited by 209
Positive and Negative Roles of p85α and p85β Regulatory Subunits of Phosphoinositide 3-Kinase in Insulin Signaling
Ueki, K., Fruman, D. A., Yballe, C. M., Faßhauer, M., Klein, J. C., Asano, T., Cantley, L. C., & Kahn, C. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m305602200 · Cited by 209
Retracted
HMBA Releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and Activates HIV Transcription
Contreras, X., Barborič, M., Lenasi, T., & Peterlin, B. M. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030146 · Cited by 215
Free and nanoencapsulated curcumin suppress β-amyloid-induced cognitive impairments in rats: Involvement of BDNF and Akt/GSK-3β signaling pathway
Hoppe, J. B., Coradini, K., Frozza, R. L., de Oliveira, C. M., Meneghetti, A., Bernardi, A., Pires, E. N. S., Beck, R. C. R., & Salbego, C. G. (2013) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2013.08.001 · Cited by 209
Epidermal growth factor family of receptors in preneoplasia and lung cancer: perspectives for targeted therapies
Hirsch, F. R., Scagliotti, G. V., Langer, C. J., Varella‐Garcia, M., & Franklin, W. A. (2003) · Lung Cancer · doi:10.1016/s0169-5002(03)00137-5 · Cited by 208
Constitutively Activated Akt-1 Is Vital for the Survival of Human Monocyte-Differentiated Macrophages
Liu, H., Perlman, H., Pagliari, L. J., & Pope, R. M. (2001) · The Journal of Experimental Medicine · doi:10.1084/jem.194.2.113 · Cited by 208
The costimulation-regulated duration of PKB activation controls T cell longevity
Song, J. J., Salek‐Ardakani, S., Rogers, P., Cheng, M. H.-Y., Parijs, L. V., & Croft, M. (2004) · Nature Immunology · doi:10.1038/ni1030 · Cited by 209
Akt1 Regulates a JNK Scaffold during Excitotoxic Apoptosis
Kim, A. H., Yano, H., Cho, H., Meyer, D. J., Monks, B. R., Margolis, B. L., Birnbaum, M. J., & Chao, M. V. (2002) · Neuron · doi:10.1016/s0896-6273(02)00821-8 · Cited by 204
A biochemical and functional characterization of diet‐induced brain insulin resistance
Mielke, J. G., Taghibiglou, C., Liu, L., Zhang, Y., Jia, Z., Adeli, K., & Wang, Y. T. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03155.x · Cited by 210
Proinflammatory cytokines in heart failure: double-edged swords
Hedayat, M., Mahmoudi, M. J., Rose, N. R., & Rezaei, N. (2010) · Heart Failure Reviews · doi:10.1007/s10741-010-9168-4 · Cited by 210
Lipid raft: A floating island of death or survival
George, K. S., & Wu, S. (2012) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2012.01.007 · Cited by 205
Role of vascular endothelial growth factor in the stimulation of cellular invasion and signaling of breast cancer cells.
Price, D. J., Miralem, T., Jiang, S., Steinberg, R., & Avraham, H. K. (2001) · PubMed · Cited by 206
Implications of Phosphoinositide 3-Kinase-Akt (PI3K-Akt) Pathway in the Pathogenesis of Alzheimer’s Disease
Kumar, M., & Bansal, N. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02611-7 · Cited by 208
Mechanisms by which IGF-I May Promote Cancer
Grimberg, A. (2003) · Cancer Biology & Therapy · doi:10.4161/cbt.2.6.678 · Cited by 204
Hypoxic preconditioning induces the expression of prosurvival and proangiogenic markers in mesenchymal stem cells
Chacko, S. M., Ahmed, S., Selvendiran, K., Kuppusamy, M. L., Khan, M., & Kuppusamy, P. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00221.2010 · Cited by 206
Integrin (α6β4) regulation of eIF-4E activity and VEGF translation
Chung, J., Bachelder, R. E., Lipscomb, E. A., Shaw, L. M., & Mercurio, A. M. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200112015 · Cited by 207
The Serine/Threonine Kinase PAK4 Prevents Caspase Activation and Protects Cells from Apoptosis
Gnesutta, N., Qu, J., & Minden, A. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011046200 · Cited by 204
Cell-Type Specific Integration of Cross-Talk between Extracellular Signal-Regulated Kinase and cAMP Signaling
Houslay, M. D., & Kölch, W. (2000) · Molecular Pharmacology · doi:10.1124/mol.58.4.659 · Cited by 201
Calcium regulates the PI3K‐Akt pathway in stretched osteoblasts
Danciu, T., Adam, R. M., Naruse, K., Freeman, M. R., & Hauschka, P. V. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00055-3 · Cited by 200
Apoptosis: A Basic Physiologic Process in Wound Healing
Rai, N. K., Tripathi, K., Sharma, D., & Shukla, V. K. (2005) · The International Journal of Lower Extremity Wounds · doi:10.1177/1534734605280018 · Cited by 207
Mitofusin 2 Triggers Vascular Smooth Muscle Cell Apoptosis via Mitochondrial Death Pathway
Guo, X., Chen, K., Guo, Y., Liao, H., Tang, J., & Xiao, R. (2007) · Circulation Research · doi:10.1161/circresaha.107.157644 · Cited by 201
Make Yourself at Home: Viral Hijacking of the PI3K/Akt Signaling Pathway
Diehl, N., & Schaal, H. (2013) · Viruses · doi:10.3390/v5123192 · Cited by 207
Akt1 governs breast cancer progression in vivo
Ju, X., Katiyar, S., Wang, C., Liu, M., Jiao, X., Li, S. C., Zhou, J., Turner, J., Lisanti, M. P., Russell, R. G., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605874104 · Cited by 200
Phosphatidylinositol-3-Kinase Signaling Is Required for Erythropoietin-Mediated Acute Protection Against Myocardial Ischemia/Reperfusion Injury
Cai, Z. P., & Semenza, G. L. (2004) · Circulation · doi:10.1161/01.cir.0000127954.98131.23 · Cited by 199
Host cell manipulation by the human pathogen Toxoplasma gondii
Laliberté, J., & Carruthers, V. B. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-7556-x · Cited by 199
Cell Type-specific Expression of the IκB Kinases Determines the Significance of Phosphatidylinositol 3-Kinase/Akt Signaling to NF-κB Activation
Gustin, J. A., Özeş, O. N., Akça, H., Pincheira, R., Mayo, L. D., Li, Q., Guzman, J. R., Korgaonkar, C. K., & Donner, D. B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306976200 · Cited by 199
Heterotrimeric G-protein βγ-dimers in growth and differentiation
Schwindinger, W. F., & Robishaw, J. D. (2001) · Oncogene · doi:10.1038/sj.onc.1204181 · Cited by 199
A Novel Role for the Adaptor Molecule CD2-associated Protein in Transforming Growth Factor-β-induced Apoptosis
Schiffer, M., Mundel, P. H., Shaw, A. S., & Böttinger, E. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403534200 · Cited by 198
Positive feedback regulation between AKT activation and fatty acid synthase expression in ovarian carcinoma cells
Wang, H. Q., Altomare, D. A., Skele, K. L., Poulikakos, P. I., Kuhajda, F. P., Cristofano, A. D., & Testa, J. R. (2005) · Oncogene · doi:10.1038/sj.onc.1208463 · Cited by 198
Activated Akt promotes increased resting T cell size, CD28‐independent T cell growth, and development of autoimmunity and lymphoma
Rathmell, J. C., Elstrom, R., Cinalli, R. M., & Thompson, C. B. (2003) · European Journal of Immunology · doi:10.1002/eji.200324048 · Cited by 196
Survivin Expression Is Regulated by Coexpression of Human Epidermal Growth Factor Receptor 2 and Epidermal Growth Factor Receptor via Phosphatidylinositol 3-Kinase/AKT Signaling Pathway in Breast Cancer Cells
Asanuma, H., Torigoe, T., Kamiguchi, K., Hirohashi, Y., Ohmura, T., Hirata, K., Sato, M., & Sato, N. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0491 · Cited by 196
Overcoming Drug Resistance by Enhancing Apoptosis of Tumor Cells
Gimenez‐Bonafé, P., Tortosa, A., & Pérez‐Tomás, R. (2009) · Current Cancer Drug Targets · doi:10.2174/156800909788166600 · Cited by 194
Insulin-secreting β-Cell Dysfunction Induced by Human Lipoproteins
Roehrich, M.-E., Mooser, V., Lenain, V., Herz, J., Nimpf, J., Azhar, S., Bideau, M., Capponi, A. M., NICOD, P. H., Haefliger, J., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300102200 · Cited by 193
Cancer cachexia prevention via physical exercise: molecular mechanisms
Gould, D. W., Lahart, I. M., Carmichael, A. R., Koutedakis, Y., & Metsios, G. S. (2012) · Journal of Cachexia Sarcopenia and Muscle · doi:10.1007/s13539-012-0096-0 · Cited by 200
Activation of Akt/Protein Kinase B in Epithelial Cells by theSalmonella typhimurium Effector SigD
Steele‐Mortimer, O., Knodler, L. A., Marcus, S. L., Scheid, M. P., Goh, B., Pfeifer, C. G., Duronio, V., & Finlay, B. B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m008187200 · Cited by 195
Infection of human cancer cells with myxoma virus requires Akt activation via interaction with a viral ankyrin-repeat host range factor
Wang, G., Barrett, J. W., Stanford, M. M., Werden, S. J., Johnston, J. B., Gao, X., Sun, M., Cheng, J. Q., & McFadden, G. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509341103 · Cited by 194
Ovarian Hormones Elicit Phosphorylation of Akt and Extracellular-Signal Regulated Kinase in Explants of the Cerebral Cortex
Singh, M. (2001) · Endocrine · doi:10.1385/endo:14:3:407 · Cited by 194
Ca2+-Permeable AMPA Receptors Regulate Growth of Human Glioblastoma via Akt Activation
Ishiuchi, S., Yoshida, Y., Sugawara, K., Aihara, M., Ohtani, T., Watanabe, T., Saito, N., Tsuzuki, K., Okado, H., Miwa, A., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2180-07.2007 · Cited by 193
miR-205 Targets PTEN and PHLPP2 to Augment AKT Signaling and Drive Malignant Phenotypes in Non–Small Cell Lung Cancer
Cai, J., Fang, L., Huang, Y., Li, R., Yuan, J., Yang, Y., Zhu, X., Chen, B., Wu, J., & Li, M. (2013) · Cancer Research · doi:10.1158/0008-5472.can-13-0297 · Cited by 197
Activation of Integrin-Linked Kinase Is a Critical Prosurvival Pathway Induced in Leukemic Cells by Bone Marrow–Derived Stromal Cells
Tabe, Y., Jin, L., Tsutsumi‐Ishii, Y., Xu, Y., McQueen, T. J., Priebe, W., Mills, G. B., Ohsaka, A., Nagaoka, I., Andreeff, M., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-3166 · Cited by 193
Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice
Fukao, T., Yamada, T., Tanabe, M., Terauchi, Y., Ota, T., Takayama, T., Asano, T., Takeuchi, T., Kadowaki, T., Hata, J.-I., et al. (2002) · Nature Immunology · doi:10.1038/ni768 · Cited by 193
The Bile Acid Taurochenodeoxycholate Activates a Phosphatidylinositol 3-Kinase-dependent Survival Signaling Cascade
Rust, C., Karnitz, L. M., Payá, C. V., Moscat, J., Simari, R. D., & Gores, G. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m909992199 · Cited by 193
Molecular determinants of retinal ganglion cell development, survival, and regeneration
Isenmann, S. (2003) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(03)00027-2 · Cited by 192
Akt1/Akt2 and Mammalian Target of Rapamycin/Bim Play Critical Roles in Osteoclast Differentiation and Survival, Respectively, Whereas Akt Is Dispensable for Cell Survival in Isolated Osteoclast Precursors
Sugatani, T., & Hruska, K. A. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m410480200 · Cited by 194
The Regulation of Ovarian Granulosa Cell Death by Pro- and Anti-apoptotic Molecules
MATSUDA‐MINEHATA, F., Inoue, N., Goto, Y., & MANABE, N. (2006) · Journal of Reproduction and Development · doi:10.1262/jrd.18069 · Cited by 193
Radiation-induced Akt activation modulates radioresistance in human glioblastoma cells
Li, H., Kim, J.-S., & Waldman, T. A. (2009) · Radiation Oncology · doi:10.1186/1748-717x-4-43 · Cited by 198
Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation
Resende, R., & Adhikari, A. (2009) · Cell Communication and Signaling · doi:10.1186/1478-811x-7-20 · Cited by 183
Flavonoids in modulation of cell survival signalling pathways
Mansuri, M. L., Parihar, P., Solanki, I., & Parihar, M. S. (2014) · Genes & Nutrition · doi:10.1007/s12263-014-0400-z · Cited by 189
A Cdk5 inhibitory peptide reduces tau hyperphosphorylation and apoptosis in neurons
Zheng, Y., Kesavapany, S., Gravell, M., Hamilton, R. S., Schubert, M., Amin, N. D., Albers, W., Grant, P. G., & Pant, H. C. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600441 · Cited by 190
Functional and therapeutic significance of Akt deregulation in malignant melanoma
Robertson, G. P. (2005) · Cancer and Metastasis Reviews · doi:10.1007/s10555-005-1577-9 · Cited by 187

Authors: Datta, S. R., Brunet, A., & Greenberg, M. E.
Affiliations: Boston Children's Hospital (US)
ORCID: Datta, S. R.
Brunet, A.
Greenberg, M. E.
Venue: Genes & Development
Publisher: Cold Spring Harbor Laboratory
Published: 1999-11-15
Volume: 13
Issue: 22
Pages: 2905-2927
ISSN: 0890-9369 (ISSN-L)
DOI: 10.1101/gad.13.22.2905
OpenAlex: W2147114673
Cited by: 4,216
References: 233
Citations by year: 2026: 27 · 2025: 36 · 2024: 45 · 2023: 47 · 2022: 60 · 2021: 68 · 2020: 87 · 2019: 86 · 2018: 81 · 2017: 94 · 2016: 90 · 2015: 140 · 2014: 136 · 2013: 149 · 2012: 150
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Genes & Development (publishedVersion)
PubMed (publishedVersion)
Funders: Bentham-Moxon Trust
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 › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords: cell survival, apoptosis, PI3K/Akt signaling, neurotrophins, trophic factors, developmental cell death, Bad, caspase-9, forkhead transcription factor, IκB kinase, NF-kB, neuronal survival, growth factor signaling
MeSH terms: Animals, Carrier Proteins, Cell Survival, Cell Transformation, Neoplastic, Humans, Phosphatidylinositols, Phosphorylation, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Substrate Specificity, Transcription Factors, Signal Transduction, NF-kappa B, Sequence Alignment, Apoptosis, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Phosphatidylinositol 3-Kinases, Protein Isoforms, Caspases, Glycogen Synthase Kinase 3, bcl-Associated Death Protein, Proto-Oncogene Proteins c-akt, Mice, Rats, I-kappa B Kinase, Caspase 9

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Cellular survival: a play in three Akts

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks