A signaling mechanism from Gαq-protein-coupled metabotropic glutamate receptors to gene expression: Role of the c-Jun N-Terminal kinase pathway

Lu Yang, Limin Mao, Hai Chen, Michael Catavsan, Jonathan Kozinn, Anish Arora, Xianyu Liu, John Q. Wang

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Gαq-protein-coupled group I metabotropic glutamate receptors (mGluRs) are densely expressed in brain neurons and are actively involved in various cellular activities. In this study, we investigated the role of group I mGluRs in regulating the c-Jun N-terminal kinase (JNK)/stress-activated protein kinase in cultured neurons. We found that selective activation of mGluR5 induced a rapid and transient phosphorylation of JNK. In a series of studies to determine the mechanisms, we found that the conventional mGluR5-associated signaling pathways (inositol-1,4,5-triphosphate-mediated Ca2+ release and activation of protein kinase C) were not involved in the mGluR5 regulation. Instead, ligand stimulation ofmGluR5caused a dynamic transactivation of the epidermal growth factor (EGF) receptor, which in turn triggered a downstream signaling pathway to upregulate JNK phosphorylation. Furthermore, the mGluR5-dependent JNK activation specifically activated c-Jun, but not activating transcription factor-2 or JunD, and increased activator protein-1 (AP-1)-mediated endogenous transcriptional activity. Together, we identified a novel mGluR5-to-nucleus communication through the EGF/JNK pathway, which functions to regulate AP-1-mediated transcription.

Original languageEnglish
Pages (from-to)971-980
Number of pages10
JournalJournal of Neuroscience
Volume26
Issue number3
DOIs
StatePublished - Jan 18 2006

Keywords

  • AP-1
  • EGF
  • JNK
  • Jun
  • MAPK
  • MKK
  • Nucleus accumbens
  • SAPK
  • Striatum
  • mGluR

Fingerprint

Dive into the research topics of 'A signaling mechanism from Gαq-protein-coupled metabotropic glutamate receptors to gene expression: Role of the c-Jun N-Terminal kinase pathway'. Together they form a unique fingerprint.

Cite this