TY - JOUR T1 - A Signaling Mechanism from Gαq-Protein-Coupled Metabotropic Glutamate Receptors to Gene Expression: Role of the c-Jun N-Terminal Kinase Pathway JF - The Journal of Neuroscience JO - J. Neurosci. SP - 971 LP - 980 DO - 10.1523/JNEUROSCI.4423-05.2006 VL - 26 IS - 3 AU - Lu Yang AU - Limin Mao AU - Hai Chen AU - Michael Catavsan AU - Jonathan Kozinn AU - Anish Arora AU - Xianyu Liu AU - John Q. Wang Y1 - 2006/01/18 UR - http://www.jneurosci.org/content/26/3/971.abstract N2 - 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 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. ER -