Group I metabotropic glutamate receptors control phosphorylation of CREB, Elk-1 and ERK via a CaMKII-dependent pathway in rat striatum

Neurosci Lett. 2001 Nov 9;313(3):129-32. doi: 10.1016/s0304-3940(01)02258-3.


In vivo activation of group I metabotropic glutamate receptors (mGluRs) upregulates phosphorylation of cyclic AMP response element-binding protein (CREB), Elk-1 and extracellular signal-regulated kinases (ERK) in striatal neurons. To evaluate putative roles of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in CREB, Elk-1 and ERK phosphorylation, the CaMKII inhibitor, KN62, was infused simultaneously with the group I mGluR agonist, 3,5-dihydroxyphenylglycine (DHPG), into the rat dorsal striatum. The results showed that DHPG (125, 250, and 500 nmol) increased phosphorylated (p) CaMKII immunoreactivity (IR) in a dose-dependent manner. KN62 (50 nmol) significantly attenuated 500 nmol DHPG-induced pERK, pElk-1 and pCREB IR in the ipsilateral dorsal striatum. These data indicate that pCaMKII is a possible upstream effector that is responsible for the regulation of CREB, Elk-1 and ERK phosphoproteins in response to group I mGluR stimulation in striatal neurons.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • DNA-Binding Proteins*
  • Enzyme Inhibitors / pharmacology
  • Excitatory Amino Acid Agonists / pharmacology
  • Glycine / analogs & derivatives
  • Glycine / pharmacology
  • Immunohistochemistry
  • Male
  • Microinjections
  • Mitogen-Activated Protein Kinases / metabolism*
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Metabotropic Glutamate / agonists
  • Receptors, Metabotropic Glutamate / metabolism*
  • Resorcinols / pharmacology
  • Signal Transduction / physiology
  • Transcription Factors*
  • ets-Domain Protein Elk-1


  • Cyclic AMP Response Element-Binding Protein
  • DNA-Binding Proteins
  • Elk1 protein, rat
  • Enzyme Inhibitors
  • Excitatory Amino Acid Agonists
  • Proto-Oncogene Proteins
  • Receptors, Metabotropic Glutamate
  • Resorcinols
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • 3,5-dihydroxyphenylglycine
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Glycine