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NR2B-NMDA receptor-mediated increases in intracellular Ca2+ concentration regulate the tyrosine phosphatase, STEP, and ERK MAP kinase signaling
| Content Provider | Scilit |
|---|---|
| Author | Paul, Surojit Connor, John A. |
| Copyright Year | 2010 |
| Description | Journal: Journal of Neurochemistry J. Neurochem. (2010) 114, 1107–1118. 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. |
| Related Links | http://europepmc.org/articles/pmc3049732?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049732/pdf https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1471-4159.2010.06835.x |
| Ending Page | 1118 |
| Page Count | 12 |
| Starting Page | 1107 |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.2010.06835.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 4 |
| Volume Number | 114 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 2010-06-28 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Extracellular‐regulated Kinase Striatal‐enriched Phosphatase Tyrosine Phosphatase |
| Content Type | Text |
| Resource Type | Article |
