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Cyclic AMP Promotes Neuronal Survival by Phosphorylation of Glycogen Synthase Kinase 3β
Open accessAbstract
Agents that elevate intracellular cyclic AMP (cAMP) levels promote neuronal survival in a manner independent of neurotrophic factors. Inhibitors of phosphatidylinositol 3 kinase and dominant-inactive mutants of the protein kinase Akt do not block the survival effects of cAMP, suggesting that another signaling pathway is involved. In this report, we demonstrate that elevation of intracellular cAMP levels in rat cerebellar granule neurons leads to phosphorylation and inhibition of glycogen synthase kinase 3beta (GSK-3beta). The increased phosphorylation of GSK-3beta by protein kinase A (PKA) occurs at serine 9, the same site phosphorylated by Akt. Purified PKA is able to phosphorylate recombinant GSK-3beta in vitro. Inhibitors of GSK-3 block apoptosis in these neurons, and transfection of neurons with a GSK-3beta mutant that cannot be phosphorylated interferes with the prosurvival effects of cAMP. These data suggest that activated PKA directly phosphorylates GSK-3beta and inhibits its apoptotic activity in neurons.
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Cites
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
Trophic factors and neuronal survival
Barde, Y.-A. (1989) · Neuron · doi:10.1016/0896-6273(89)90040-8 · Cited by 1,625
Cited by
GSK-3: tricks of the trade for a multi-tasking kinase
Doble, B. W., & Woodgett, J. R. (2003) · Journal of Cell Science · doi:10.1242/jcs.00384 · Cited by 2,084
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
GSK3 takes centre stage more than 20 years after its discovery
FRAME, S., & COHEN, P. (2001) · Biochemical Journal · doi:10.1042/0264-6021:3590001 · Cited by 1,433
Role of tau protein in both physiological and pathological conditions
AVILA, J., LUCAS, J. J., PÉREZ, M., & HERNÁNDEZ, F. (2004) · Physiological Reviews · doi:10.1152/physrev.00024.2003 · Cited by 1,005
GSK-3: Functional Insights from Cell Biology and Animal Models
Kaidanovich-Beilin, O., & Woodgett, J. R. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00040 · Cited by 485
Metadata
- Authors
- Li, M., Wang, X., Meintzer, M. K., Laessig, T., Birnbaum, M. J., & Heidenreich, K. A.
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2000-12-01
- Volume
- 20
- Issue
- 24
- Pages
- 9356-9363
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- OpenAlex
- W2122807946
- Cited by
- 363
- References
- 2
- FWCI
- 8.22
- Type
- journal article
- Language
- en
- Open access
- green
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- Li, M., Wang, X., Meintzer, M. K., Laessig, T., Birnbaum, M. J., & Heidenreich, K. A. (2000). Cyclic AMP Promotes Neuronal Survival by Phosphorylation of Glycogen Synthase Kinase 3β. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.20.24.9356-9363.2000
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