Cited by 225Nerve injury and regenerationPI3K/AKT/mTOR signaling in cancerGrowth Hormone and Insulin-like Growth Factors

The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.

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, Wen‐Hua, Quirion, Rémi·2004·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2004.02350.x

Open this paper in CoChat — free account

Abstract

Insulin-like growth factor-1 (IGF-1) and brain-derived neurotrophic factor (BDNF) are trophic factors required for the viability and normal functions of various neuronal cells. However, the detailed intracellular mechanism(s) involved in these effects in neuronal cells remains to be fully elucidated. In present study, the respective intracellular signaling pathway induced by IGF-1 and BDNF and their possible role in neuronal survival were investigated. Both IGF-1 and BDNF protected hippocampal neurons from serum deprivation-induced death with IGF-1 apparently being more potent. Western blot analyses showed that both IGF-1 and BDNF induced the activation of the phosphatidylinositide 3 kinase (PI3)/Akt (protein kinase B) kinase and the mitogen-activated protein kinase (MAPK) pathways. The phosphorylation of Akt and its downstream target, FKHRL1, induced by IGF-1 was rapid and sustained while that of MAPK was transient. The reverse situation was observed for BDNF. Moreover, IGF-1 potently induced the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and its association with PI3 kinase while BDNF was weak in these assays. In contrast, the tyrosine phosphorylation of Shc proteins was dramatically stimulated by BDNF, with IGF-1 having only a minimal effect. Most interestingly, only the inhibitor of the PI3K/Akt pathway, LY294002, was able to block the survival effects of both IGF-1 and BDNF; an inhibitor of the MAPK pathway inhibitor, PD98059, being ineffective. Taken together, these data reveal that the survival properties of both IGF-1 and BDNF against serum deprivation are mediated by the activation of the PI3K/Akt, but not the MAPK, pathway in hippocampal neurons.

Integrity signals

Registry

Crossref · 10.1111/j.1471-4159.2004.02350.x

Cites

44 of 44 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

The phosphatidylinositol 3-Kinase–AKT pathway in human cancer
Vivanco, I., & Sawyers, C. L. (2002) · Nature reviews. Cancer · doi:10.1038/nrc839 · Cited by 6,155
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
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
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 3,014
Regulation of Cell Death Protease Caspase-9 by Phosphorylation
Cardone, M. H., Roy, N., Stennicke, H. R., Salvesen, G. S., Franke, T. F., Stanbridge, E., Frisch, S., & Reed, J. C. (1998) · Science · doi:10.1126/science.282.5392.1318 · Cited by 2,481
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
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
Cell Survival Promoted by the Ras-MAPK Signaling Pathway by Transcription-Dependent and -Independent Mechanisms
Bonni, A., Brunet, A., West, A. E., Datta, S. R., Takasu, M. A., & Greenberg, M. E. (1999) · Science · doi:10.1126/science.286.5443.1358 · Cited by 1,908
Interleukin-3-Induced Phosphorylation of BAD Through the Protein Kinase Akt
Peso, L. D., González-Garcı́a, M., Page, C., Herrera, R., & Nuñez, G. (1997) · Science · doi:10.1126/science.278.5338.687 · Cited by 1,797
Molecular and Cellular Aspects of the Insulin-Like Growth Factor I Receptor
LeRoith, D., Werner, H., Beitner‐Johnson, D., & Roberts, C. T. (1995) · Endocrine Reviews · doi:10.1210/edrv-16-2-143 · Cited by 1,424
Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase
Delcommenne, M., Tan, C., Gray, V., Rue, L., Woodgett, J. R., & Dedhar, S. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.19.11211 · Cited by 1,102
Circulating Insulin-Like Growth Factor I Mediates Exercise-Induced Increases in the Number of New Neurons in the Adult Hippocampus
Trejo, J. L., Carro, E., & Torres-Alemán, I. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-05-01628.2001 · Cited by 1,017
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
Mitogen-activated protein kinase cascades and regulation of gene expression
Su, B., & Karin, M. (1996) · Current Opinion in Immunology · doi:10.1016/s0952-7915(96)80131-2 · Cited by 747
Akt Phosphorylates and Negatively Regulates Apoptosis Signal-Regulating Kinase 1
Kim, A. H., Khursigara, G., Sun, X., Franke, T. F., & Chao, M. V. (2001) · Molecular and Cellular Biology · doi:10.1128/mcb.21.3.893-901.2001 · Cited by 716
trkB, a novel tyrosine protein kinase receptor expressed during mouse neural development.
Klein, R., Parada, L. F., Coulier, F., & Barbacid, M. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb08545.x · Cited by 598
Neurotrophic factors and their receptors.
Barbacid, M. (1995) · Current Opinion in Cell Biology · doi:10.1016/0955-0674(95)80022-0 · Cited by 577
Phosphorylation of Serine 256 by Protein Kinase B Disrupts Transactivation by FKHR and Mediates Effects of Insulin on Insulin-like Growth Factor-binding Protein-1 Promoter Activity through a Conserved Insulin Response Sequence
Guo, S., Rena, G., Cichy, S. B., He, X., Cohen, P., & Unterman, T. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.24.17184 · Cited by 540
The role of neuronal growth factors in neurodegenerative disorders of the human brain
Connor, B. J., & Dragunow, M. (1998) · Brain Research Reviews · doi:10.1016/s0165-0173(98)00004-6 · Cited by 538
PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2
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
IRS-1 is a common element in insulin and insulin-like growth factor-I signaling to the phosphatidylinositol 3'-kinase
Myers, M. G., Sun, X., Cheatham, B., Jachna, B. R., Glasheen, E. M., Backer, J., & White, M. F. (1993) · Endocrinology · doi:10.1210/endo.132.4.8384986 · Cited by 335
Requirement for Activation of the Serine-Threonine Kinase Akt (Protein Kinase B) in Insulin Stimulation of Protein Synthesis but Not of Glucose Transport
Kitamura, T., Ogawa, W., Sakaue, H., Hino, Y., Kuroda, S., Takata, M., Matsumoto, M., Maeda, T., Konishi, H., Kikkawa, U., et al. (1998) · Molecular and Cellular Biology · doi:10.1128/mcb.18.7.3708 · Cited by 328
Insulin-like growth factor I protects and rescues hippocampal neurons against β-amyloid- and human amylin-induced toxicity
Doré, S., Kar, S., & Quirion, R. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4772 · Cited by 325
Self-citation
Evidence for a functional role of Shc proteins in mitogenic signaling induced by insulin, insulin-like growth factor-1, and epidermal growth factor.
Sasaoka, T., Rose, D. W., Jhun, B. H., Saltiel, A. R., Draznin, B., & Olefsky, J. M. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)36885-0 · Cited by 287
Insulin-like growth factor-I receptor signal transduction: at the interface between physiology and cell biology
Butler, A. A., Yakar, S., Gewolb, I. H., Karas, M., Okubo, Y., & LeRoith, D. (1998) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/s0305-0491(98)10106-2 · Cited by 252
Not all Shc's roads lead to Ras
Bonfini, L., Migliaccio, E., Pelicci, G., Lanfrancone, L., & Pelicci, P. G. (1996) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(96)10033-5 · Cited by 244
Insulin-Like Growth Factor-I Is a Differentiation Factor for Postmitotic CNS Stem Cell-Derived Neuronal Precursors: Distinct Actions from Those of Brain-Derived Neurotrophic Factor
Arsenijevic, Y., & Weiss, S. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-06-02118.1998 · Cited by 243
Akt Activation Protects Hippocampal Neurons from Apoptosis by Inhibiting Transcriptional Activity of p53
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
Differential Signaling by Insulin Receptor Substrate 1 (IRS-1) and IRS-2 in IRS-1-Deficient Cells
Brüning, J. C., Winnay, J. N., Cheatham, B., & Kahn, C. R. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.3.1513 · Cited by 206
Autocrine—paracrine Regulation of Hippocampal Neuron Survival by IGF‐1 and the Neurotrophins BDNF, NT‐3 and NT‐4
Lindholm, D., Carroll, P., Tzimagiorgis, G., & Thoenen, H. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01607.x · Cited by 180
The synergistic effects of NGF and IGF‐1 on neurite growth in adult sensory neurons: convergence on the PI 3‐kinase signaling pathway
Jones, D. M., Tucker, B. A., Rahimtula, M., & Mearow, K. M. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01925.x · Cited by 176
Insulin-Like Growth Factor-1–Induced Phosphorylation of Transcription Factor FKHRL1 Is Mediated by Phosphatidylinositol 3-Kinase/Akt Kinase and Role of This Pathway in Insulin-Like Growth Factor-1–Induced Survival of Cultured Hippocampal Neurons
Zheng, W., Kar, S., & Quirion, R. (2002) · Molecular Pharmacology · doi:10.1124/mol.62.2.225 · Cited by 164
Self-citation
Insulin-like Growth Factor-1-induced Phosphorylation of the Forkhead Family Transcription Factor FKHRL1 Is Mediated by Akt Kinase in PC12 Cells
Zheng, W., Kar, S., & Quirion, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002417200 · Cited by 153
Self-citation
Activation of Phosphatidylinositol 3‐Kinase, but Not Extracellular‐Regulated Kinases, Is Necessary to Mediate Brain‐Derived Neurotrophic Factor‐Induced Motoneuron Survival
Dolcet, X., Egea, J., Soler, R. M., Martı́n-Zanca, D., & Comella, J. X. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0730521.x · Cited by 127
Insulin-like growth factor-1 (IGF-1): a neuroprotective trophic factor acting via the Akt kinase pathway
Zheng, W., Kar, S., Doré, S., & Quirion, R. (2000) · Springer eBooks · doi:10.1007/978-3-7091-6301-6_17 · Cited by 122
Self-citation
Comparison of the insulin and insulin-like growth factor 1 mitogenic intracellular signaling pathways
Sasaoka, T., Ishiki, M., Sawa, T., Ishihara, H., Takata, Y., Imamura, T., Usui, I., Olefsky, J. M., & Kobayashi, M. (1996) · Endocrinology · doi:10.1210/endo.137.10.8828504 · Cited by 119
Differences in survival‐promoting effects and intracellular signaling properties of BDNF and IGF‐1 in cultured cerebral cortical neurons
Yamada, M., Tanabe, K., Wada, K., Shimoke, K., Ishikawa, Y., Ikeuchi, T., Koizumi, S., & Hatanaka, H. (2001) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2001.00497.x · Cited by 108
FKHRL1 and its homologs are new targets of nerve growth factor Trk receptor signaling
Zheng, W., Kar, S., & Quirion, R. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00783.x · Cited by 96
Self-citation
Insulin-like growth factor-1 attenuates apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats.
Tagami, M., Ikeda, K., Nara, Y., Fujino, H., Kubota, A., Numano, F., & Yamori, Y. (1997) · PubMed · Cited by 79
Stimulation of Protein Kinase C Modulates Insulin-like Growth Factor-1-induced Akt Activation in PC12 Cells
Zheng, W., Kar, S., & Quirion, R. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.18.13377 · Cited by 68
Self-citation
The Survival of Sympathetic Neurons Promoted by Potassium Depolarization, but Not by Cyclic AMP, Requires Phosphatidylinositol 3-Kinase and Akt
Crowder, R. J., & Freeman, R. S. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.730466.x · Cited by 56
Inhibition of protein phosphatases induces IGF‐1‐blocked neurotrophin‐insensitive neuronal apoptosis
Fernández‐Sánchez, M. T., García-Rodríguez, A., Dı́az-Trelles, R., & Novelli, A. (1996) · FEBS Letters · doi:10.1016/s0014-5793(96)01192-1 · Cited by 48
Functional Roles of the Shc Phosphotyrosine Binding and Src Homology 2 Domains in Insulin and Epidermal Growth Factor Signaling
Ricketts, W. A., Rose, D. W., Shoelson, S. E., & Olefsky, J. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.42.26165 · Cited by 47
Role of Protein Kinase C α in Nerve Growth Factor‐Induced Arachidonic Acid Release from PC12 Cells
Zheng, W., Fink, D. W., & Guroff, G. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66051868.x · Cited by 35
Self-citation

Research works printed but not linked: 1

10.1210/en.137.10.4427 · DOI

Sorted by citations

Exercise builds brain health: key roles of growth factor cascades and inflammation
Cotman, C. W., Berchtold, N. C., & Christie, L.-A. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.06.011 · Cited by 2,268
Excitotoxicity and stroke: Identifying novel targets for neuroprotection
Lai, T. W., Zhang, S., & Wang, Y. T. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.11.006 · Cited by 1,106
A simple role for BDNF in learning and memory?
Cunha, C. (2010) · Frontiers in Molecular Neuroscience · doi:10.3389/neuro.02.001.2010 · Cited by 830
Partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
Tropea, D., Giacometti, E., Wilson, N. R., Beard, C., McCurry, C., Fu, D. D., Flannery, R., Jaenisch, R., & Sur, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0812394106 · Cited by 593
Environmental enrichment and voluntary exercise massively increase neurogenesis in the adult hippocampus via dissociable pathways
Olson, A. K., Eadie, B. D., Ernst, C., & Christie, B. R. (2006) · Hippocampus · doi:10.1002/hipo.20157 · Cited by 592

See all 225

Authors: Zheng, W., & Quirion, R.
Affiliations: Douglas Mental Health University Institute (CA)
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2004-04-13
Volume: 89
Issue: 4
Pages: 844-852
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2004.02350.x
OpenAlex: W2031452891
Cited by: 225
References: 44
Citations by year: 2026: 6 · 2025: 10 · 2024: 3 · 2023: 6 · 2022: 11 · 2021: 18 · 2020: 8 · 2019: 12 · 2018: 3 · 2017: 9 · 2016: 8 · 2015: 10 · 2014: 11 · 2013: 17 · 2012: 19
FWCI: 4.81
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Canadian Institutes of Health Research
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords: insulin-like growth factor I, brain-derived neurotrophic factor, hippocampal neurons, neuronal survival, PI3K/Akt signaling, MAPK signaling, serum deprivation, Akt phosphorylation, FKHRL1, IRS-1, Shc, trophic factors, LY294002, PD98059
MeSH terms: Src Homology 2 Domain-Containing, Transforming Protein 1, Animals, Cell Survival, Cells, Cultured, Enzyme Inhibitors, Hippocampus, Insulin-Like Growth Factor I, Neurons, Phosphoproteins, Phosphorylation, Proto-Oncogene Proteins, Signal Transduction, Culture Media, Serum-Free, Rats, Sprague-Dawley, Protein Serine-Threonine Kinases, Brain-Derived Neurotrophic Factor, Phosphatidylinositol 3-Kinases, Adaptor Proteins, Vesicular Transport, Adaptor Proteins, Signal Transducing, Proto-Oncogene Proteins c-akt, Rats, Insulin Receptor Substrate Proteins, Shc Signaling Adaptor Proteins

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

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks