ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Insulin-like growth factor 1 inhibits extracellular signal-regulated kinase to promote neuronal survival via the phosphatidylinositol 3-kinase/protein kinase A/c-Raf pathway.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 88 citations in OpenAlex.
- Neuronal IL-18 Signaling in the Medial Habenula Contributes to Schizophrenia-Like Behavioral Deficits via ERK-Associated BDNF Suppression.Molecular neurobiology · 2026Article
- Loss of Dact2 alleviates cisplatin-induced nephrotoxicity through regulation of the Igfl-MAPK pathway axis.Cell biology and toxicology · 2023Article
- Consequences of oxygen deprivation on myelination and sex-dependent alterations.Molecular and cellular neurosciences · 2023Review
- BRAF activation by metabolic stress promotes glycolysis sensitizing NRASNature communications · 2022Article
- Oligodendrocyte Response to Pathophysiological Conditions Triggered by Episode of Perinatal Hypoxia-Ischemia: Role of IGF-1 Secretion by Glial Cells.Molecular neurobiology · 2020Article
- IGF1R regulates retrograde axonal transport of signalling endosomes in motor neurons.EMBO reports · 2020Article
- Insulin-like growth factor 1 modulates the phosphorylation, expression, and activity of organic anion transporter 3 through protein kinase A signaling pathway.Acta pharmaceutica Sinica. B · 2020Article
- Cholecystokinin type B receptor-mediated inhibition of A-type KCell communication and signaling : CCS · 2019Article
- Activation of Protein Kinase A Stimulates SUMOylation, Expression, and Transport Activity of Organic Anion Transporter 3.The AAPS journal · 2019Article
- P2X7 Nucleotide and EGF Receptors Exert Dual Modulation of the Dual-Specificity Phosphatase 6 (MKP-3) in Granule Neurons and Astrocytes, Contributing to Negative Feedback on ERK Signaling.Frontiers in molecular neuroscience · 2017Article
- Involvement of PI3K/Akt/FoxO3a and PKA/CREB Signaling Pathways in the Protective Effect of Fluoxetine Against Corticosterone-Induced Cytotoxicity in PC12 Cells.Journal of molecular neuroscience : MN · 2016Article
- Advancing the understanding of autism disease mechanisms through genetics.Nature medicine · 2016Review
- IGF-1R Reduction Triggers Neuroprotective Signaling Pathways in Spinal Muscular Atrophy Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Delineating the factors and cellular mechanisms involved in the survival of cerebellar granule neurons.Cerebellum (London, England) · 2015Review
- Superoxide anion radicals induce IGF-1 resistance through concomitant activation of PTP1B and PTEN.EMBO molecular medicine · 2015Article
- Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression.Cell stem cell · 2014Article
- Yin and Yang of PDGF-mediated signaling pathway in the context of HIV infection and drug abuse.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2014Review
- Acute resveratrol treatment modulates multiple signaling pathways in the ischemic brain.Neurochemical research · 2012Article
- Neurodevelopmental effects of insulin-like growth factor signaling.Frontiers in neuroendocrinology · 2012Review
- Platelet-derived growth factor CC-mediated neuroprotection against HIV Tat involves TRPC-mediated inactivation of GSK 3beta.PloS one · 2012Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extracellular signal-regulated kinase (ERK) activation has been shown to promote neuronal death in various paradigms. We demonstrated previously that the late and sustained ERK activation in cerebellar granule neurons (CGNs) cultured in low potassium predominantly promotes plasma membrane (PM) damage. Here, we examined the effects of a well established neuronal survival factor, insulin-like growth factor 1 (IGF-1), on the ERK cell death pathway. Stimulation of CGNs with IGF-1 induced an early and transient ERK activation but abrogated the appearance of late and sustained ERK. Withdrawal or readdition of IGF-1 after 4 h in low potassium failed to prevent sustained ERK activation and cell death. IGF-1 activated the protein kinase A (PKA) to mediate ERK inhibition via c-Raf phosphorylation at an inhibitory site (Ser259). Phosphatidylinositol 3-kinase (PI3K) or PKA inhibitors, but not a specific Akt inhibitor, abrogated PKA signaling. This suggests that the PI3K/PKA/c-Raf-Ser259 pathway mediates ERK inhibition by IGF-1 independent of Akt. In addition, adenoviral-mediated expression of constitutively active MEK (mitogen-activated protein kinase kinase) or Sindbis viral-mediated expression of mutant Raf Ser259Ala both attenuated IGF-1-mediated prevention of PM damage. Activation of caspase-3 promoted DNA damage. Its inhibition by IGF-1 was both PI3K and Akt dependent but PKA independent. 8-Br-cAMP, an activator of PKA, induced phosphorylation of c-Raf-Ser259 and inhibited ERK activation without affecting caspase-3. This indicates a selective role for PKA in ERK inhibition through c-Raf-Ser259 phosphorylation. Together, these data demonstrate that IGF-1 can positively and negatively regulate the ERK pathway in the same neuronal cell, and provide new insights into the PI3K/Akt/PKA signaling pathways in IGF-1-mediated neuronal survival.
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