ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2001
Differential regulation of mitogen-activated protein kinases ERK1/2 and ERK5 by neurotrophins, neuronal activity, and cAMP in neurons.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
72 citing papers in PubMed, 194 citations in OpenAlex.
- M1 muscarinic receptor modulation drives sex-specific alterations of Alzheimer's pathophysiology in APPswe/PSEN1ΔE9 mice.The Journal of pharmacology and experimental therapeutics · 2026Article
- MEK Inhibition in Glioblastoma: Current Perspectives and Future Directions.International journal of molecular sciences · 2025Review
- Disruption of Extracellular Signal-Regulated Kinase Partially Mediates Neonatal Isoflurane Anesthesia-Induced Changes in Dendritic Spines and Cognitive Function in Juvenile Mice.International journal of molecular sciences · 2025Article
- Candidate Key Proteins in Tinnitus-A Bioinformatic Study of Synaptic Transmission in the Cochlear Nucleus.Biomedicines · 2024Article
- Review
- Article
- TIMP-2 regulates 5-Fu resistance via the ERK/MAPK signaling pathway in colorectal cancer.Aging · 2022Article
- DNA Polymerase Iota Promotes Esophageal Squamous Cell Carcinoma Proliferation Through Erk-OGT-Induced G6PD Overactivation.Frontiers in oncology · 2021Article
- Playing the Whack-A-Mole Game: ERK5 Activation Emerges Among the Resistance Mechanisms to RAF-MEK1/2-ERK1/2- Targeted Therapy.Frontiers in cell and developmental biology · 2021Review
- Decreased Myocyte Enhancer Factor 2 Levels in the Hippocampus of Huntington's Disease Mice Are Related to Cognitive Dysfunction.Molecular neurobiology · 2020Article
- Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer.International journal of molecular sciences · 2020Review
- Non-'classical' MEKs: A review of MEK3-7 inhibitors.Bioorganic & medicinal chemistry letters · 2020Review
- Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy.International journal of molecular sciences · 2020Review
- Long-term Surgical and Chemical Castration Deteriorates Memory Function Through Downregulation of PKA/CREB/BDNF and c-Raf/MEK/ERK Pathways in Hippocampus.International neurourology journal · 2019Article
- Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression.Psychopharmacology · 2018Review
- BDNF activates an NFI-dependent neurodevelopmental timing program by sequestering NFATc4.Molecular biology of the cell · 2018Article
- Neurotrophin Signaling and Stem Cells-Implications for Neurodegenerative Diseases and Stem Cell Therapy.Molecular neurobiology · 2017Review
- Oncogenic signaling of MEK5-ERK5.Cancer letters · 2017Review
- IL-1β impairs retrograde flow of BDNF signaling by attenuating endosome trafficking.Journal of neuroinflammation · 2017Article
- Severe chronic cerebral hypoperfusion induces microglial dysfunction leading to memory loss in APPswe/PS1 mice.Oncotarget · 2016Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Activation of the extracellular signal-regulated kinase 1 (ERK1) and ERK2 by neurotrophins, neuronal activity, or cAMP has been strongly implicated in differentiation, survival, and adaptive responses of neurons during development and in the adult brain. Recently, a new member of the mitogen-activated protein (MAP) kinase family, ERK5, was discovered. Like ERK1 and ERK2, ERK5 is expressed in neurons, and ERK5 stimulation by epidermal growth factor is blocked by the MAP kinase/ERK kinase 1 (MEK1) inhibitors PD98059 and U0126. This suggests the interesting possibility that some of the functions attributed to ERK1/2 may be mediated by ERK5. However, the regulatory properties of ERK5 in primary cultured neurons have not been reported. Here we examined the regulation of ERK5 signaling in primary cultured cortical neurons. Our data demonstrate that, similar to ERK1/2, ERK5 is activated by neurotrophins including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and NT-4. BDNF stimulation of ERK5 required the activity of MEK5. Surprisingly, ERK5 was not stimulated by cAMP or neuronal activity induced by glutamate or membrane depolarization. In contrast to ERK1/2, ERK5 strongly activated the transcriptional activity of myocyte enhancer factor 2C (MEF2C) in pheochromocytoma 12 (PC12) cells and was required for neurotrophin stimulation of MEF2C transcription in both PC12 cells and cortical neurons. Furthermore, ERK1/2, but not ERK5, induced transcription from Elk1 and the cAMP/ Ca(2+) response element in PC12 cells. Our data suggest that mechanisms for regulation of ERK5 and downstream transcriptional pathways regulated by ERK5 are distinct from those of ERK1/2 in neurons. Furthermore, ERK5 is the first MAP kinase identified whose activity is stimulated by neurotrophins but not by neuronal activity.
Indexed as
Identifiers
11160424PMC6763829W1783361713What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.