A signaling mechanism from G alpha q-protein-coupled metabotropic glutamate receptors to gene expression: Role of the c-Jun N-terminal kinase pathway

作者：Yang L; Mao LM; Chen H; Catavsan M; Kozinn J; Arora A; Liu XY; Wang JQ^*

来源：Journal of Neuroscience, 2006, 26(3): 971-980.

DOI：10.1523/JNEUROSCI.4423-05.2006

• mGluR
• MAPK
• JNK
• SAPK
• Jun
• MKK
• AP-1
• EGF
• striatum
• nucleus accumbens

G alpha q-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 of mGluR5 caused 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.

• 出版日期2006-1-18