Activation of the extracellular signal-regulated kinase 2 by metabotropic glutamate receptors - PubMed (original) (raw)
Activation of the extracellular signal-regulated kinase 2 by metabotropic glutamate receptors
F Ferraguti et al. Eur J Neurosci. 1999 Jun.
Abstract
Activation of metabotropic glutamate receptors (mGluRs) leads to modulation of a variety of second messenger pathways probably including the mitogen-activated protein kinase (MAPK) extracellular signal-regulated protein kinases (ERK). MAPK play a key role in the control of cellular responses to changes in the external environment by regulating transcriptional activity and the phosphorylation state of several cytoplasmic targets. In this study, Chinese hamster ovary (CHO) cells permanently transfected with rat mGluR1a, mGluR2 and mGluR4 were employed as a model to examine the activation of MAPK by glutamate through mGluRs. All three mGluR subtypes rapidly stimulated ERK activation. In particular, mGluR1a and mGluR2 preferentially mediated phosphorylation and activation of ERK2 in a pertussis toxin (PTX)-sensitive and concentration-dependent manner. The activation was blocked completely by pretreatment with the antagonist (rs)-alpha-methyl-4-carboxyphenylglycine (MCPG) or with the MEK inhibitor PD098059. Furthermore, mGluR1a-mediated ERK activation was suppressed by the depletion of endogenous protein kinase C (PKC) activity and by the PKC inhibitors staurosporine and calphostin C, but not chelerythrine. When cAMP was elevated in mGluR2-expressing cells, by forskolin or dibutyryl-cAMP, slight elevation of ERK activity was observed. However, glutamate-stimulated ERK activation remained unaffected. In these cells, the phosphatidylinositol 3 kinase (PI3K) inhibitor wortmannin produced a significant, albeit only partial, inhibition of mGluR2-mediated ERK activation. These findings raise the possibility of a MAPK cascade involvement in glutamate-dependent neuronal plasticity mediated through stimulation of mGluRs.
Similar articles
- Molecular pathways mediating activation by kainate of mitogen-activated protein kinase in oligodendrocyte progenitors.
Liu HN, Larocca JN, Almazan G. Liu HN, et al. Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):50-61. doi: 10.1016/s0169-328x(99)00009-1. Brain Res Mol Brain Res. 1999. PMID: 10095077 - Structural analysis of the MAP kinase ERK2 and studies of MAP kinase regulatory pathways.
Cobb MH, Xu S, Cheng M, Ebert D, Robbins D, Goldsmith E, Robinson M. Cobb MH, et al. Adv Pharmacol. 1996;36:49-65. doi: 10.1016/s1054-3589(08)60576-1. Adv Pharmacol. 1996. PMID: 8783554 Review. No abstract available. - Regulation of the ERK subgroup of MAP kinase cascades through G protein-coupled receptors.
Sugden PH, Clerk A. Sugden PH, et al. Cell Signal. 1997 Aug;9(5):337-51. doi: 10.1016/s0898-6568(96)00191-x. Cell Signal. 1997. PMID: 9376213 Review.
Cited by
- Extracellular signal-regulated kinase 1/2 is required for the induction of group I metabotropic glutamate receptor-mediated epileptiform discharges.
Zhao W, Bianchi R, Wang M, Wong RK. Zhao W, et al. J Neurosci. 2004 Jan 7;24(1):76-84. doi: 10.1523/JNEUROSCI.4515-03.2004. J Neurosci. 2004. PMID: 14715940 Free PMC article. - BDNF protects the neonatal brain from hypoxic-ischemic injury in vivo via the ERK pathway.
Han BH, Holtzman DM. Han BH, et al. J Neurosci. 2000 Aug 1;20(15):5775-81. doi: 10.1523/JNEUROSCI.20-15-05775.2000. J Neurosci. 2000. PMID: 10908618 Free PMC article. - G-protein-coupled receptors and melanoma.
Lee HJ, Wall B, Chen S. Lee HJ, et al. Pigment Cell Melanoma Res. 2008 Aug;21(4):415-28. doi: 10.1111/j.1755-148X.2008.00478.x. Epub 2008 May 27. Pigment Cell Melanoma Res. 2008. PMID: 18582227 Free PMC article. Review. - Reduced juvenile long-term depression in tuberous sclerosis complex is mitigated in adults by compensatory recruitment of mGluR5 and Erk signaling.
Potter WB, Basu T, O'Riordan KJ, Kirchner A, Rutecki P, Burger C, Roopra A. Potter WB, et al. PLoS Biol. 2013;11(8):e1001627. doi: 10.1371/journal.pbio.1001627. Epub 2013 Aug 13. PLoS Biol. 2013. PMID: 23966835 Free PMC article. - Pertussis toxin-sensitive signaling of melanocortin-4 receptors in hypothalamic GT1-7 cells defines agouti-related protein as a biased agonist.
Büch TR, Heling D, Damm E, Gudermann T, Breit A. Büch TR, et al. J Biol Chem. 2009 Sep 25;284(39):26411-20. doi: 10.1074/jbc.M109.039339. Epub 2009 Jul 31. J Biol Chem. 2009. PMID: 19648111 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous