ArticleJournal of neurochemistry2010
NR2B-NMDA receptor-mediated increases in intracellular Ca2+ concentration regulate the tyrosine phosphatase, STEP, and ERK MAP kinase signaling.
Article in Journal of neurochemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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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.
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Who cites it
50 citing papers in PubMed, 86 citations in OpenAlex.
- LUMIN: an automated graphical analysis toolbox for high-throughput calcium imaging of in vitro neuronal cultures.Scientific reports · 2026Article
- Regulating the NMDA/NR2B signaling pathway mediates anticonvulsant, antineuroinflammation, and anti-oxidative stress effects of 1,3,benzothiazole derivative 1M in pentylenetetrazole-induced kindling in mice.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Sodium Houttuyfonate Prevents Seizures and Neuronal Cell Loss by Maintaining Glutamatergic System Stability in Male Rats with Kainic Acid-Induced Seizures.Biomedicines · 2024Article
- Are There Lipid Membrane-Domain Subtypes in Neurons with Different Roles in Calcium Signaling?Molecules (Basel, Switzerland) · 2023Review
- Uncovering the Significance of STEP61 in Alzheimer's Disease: Structure, Substrates, and Interactome.Cellular and molecular neurobiology · 2023Review
- Calcineurin-mediated dephosphorylation enhances the stability and transactivation of c-Myc.Scientific reports · 2023Article
- NMDA Receptor and Its Emerging Role in Cancer.International journal of molecular sciences · 2023Review
- Inhibition of Synaptic Glutamate Exocytosis and Prevention of Glutamate Neurotoxicity by Eupatilin fromInternational journal of molecular sciences · 2022Article
- BDNF as a therapeutic candidate for cocaine use disorders.Addiction neuroscience · 2022Article
- Lyciumamide A, a dimer of phenolic amide, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro.Journal of molecular histology · 2021Article
- Regulation of post-ischemic inflammatory response: A novel function of the neuronal tyrosine phosphatase STEP.Brain, behavior, and immunity · 2021Article
- Review
- The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer's Disease and Other Neurological Disorders.Frontiers in cell and developmental biology · 2021Review
- Competing mechanisms of plasticity impair compensatory responses to repetitive apnoea.The Journal of physiology · 2019Article
- GluN2A-NMDA receptor-mediated sustained CaThe Journal of biological chemistry · 2019Article
- Proteolytic Degradation of Hippocampal STEPMolecular neurobiology · 2019Article
- On the safety of repeated ketamine infusions for the treatment of depression: Effects of sex and developmental periods.Neurobiology of stress · 2018Review
- Intra-prelimbic cortical inhibition of striatal-enriched tyrosine phosphatase suppresses cocaine seeking in rats.Addiction biology · 2018Article
- Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1.Nature communications · 2017Article
- HOncotarget · 2017Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
NMDA receptors regulate both the activation and inactivation of the extracellular signal-regulated kinase (ERK) signaling cascade, a key pathway involved in neuronal plasticity and survival. This bi-directional regulation of ERK activity by NMDA receptors has been attributed to opposing actions of NR2A- versus NR2B-containing NMDA receptors, but how this is implemented is not understood. Here, we show that glutamate-mediated intracellular Ca(2+) increases occur in two phases, a rapid initial increase followed by a delayed larger increase. Both phases of the Ca(2+) increase were blocked by MK-801, a non-selective NMDA receptor inhibitor. On the other hand, selective inhibition of NR2B-NMDA receptors by Ifenprodil or Ro 25-6981 blocked the delayed larger phase but had only a small effect on the rapid initial increase. The rapid initial increase in Ca(2+), presumably because of NR2A-NMDAR activation, was sufficient to activate ERK, whereas the large delayed increases in Ca(2+) mediated by NR2B-NMDARs were necessary for dephosphorylation and subsequent activation of striatal-enriched phosphatase, a neuron-specific tyrosine phosphatase that in turn mediates the dephosphorylation and inactivation of ERK. We conclude that the magnitude of Ca(2+) increases mediated through NR2B-NMDA receptors plays a critical role in the regulation of the serine/threonine and tyrosine kinases and phosphatases that are involved in the regulation of ERK activity.
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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.