TY - JOUR T1 - Activation of Group I Metabotropic Glutamate Receptors Increases Serine Phosphorylation of GluR1 α-Amino-3-hydroxy-5-methylisoxazole-4-propionic Acid Receptors in the Rat Dorsal Striatum JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1117 LP - 1126 DO - 10.1124/jpet.108.149542 VL - 329 IS - 3 AU - Sung Min Ahn AU - Eun Sang Choe Y1 - 2009/06/01 UR - http://jpet.aspetjournals.org/content/329/3/1117.abstract N2 - Protein phosphorylation is an important mechanism for the post-translational modulation of ionotropic glutamate receptors. In this study, we investigated the regulation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor GluR1 subunit phosphorylation by the stimulation of group I metabotropic glutamate receptors (mGluRs) in the rat dorsal striatum in vivo. Stimulation of group I mGluRs was found to increase GluR1 phosphorylation of Ser831 and Ser845 in phospholipase C (PLC)-coupled Ca2+ cascades. Interactions of protein kinases activated by intracellular Ca2+ release downstream to PLC modulate the phosphorylation state of GluR1 on Ser831 and Ser845: phosphorylation of GluR1 on Ser831 is up-regulated by the protein kinase C and calcium-calmodulin-dependent protein kinase (CaMK)/c-Jun N-terminal kinase (JNK) pathways, whereas phosphorylation of GluR1 on Ser845 is up-regulated by the protein kinase A (PKA), PKA/ERK1/2, and PKA/JNK pathways. The phosphorylation state of GluR1 on Ser831 and Ser845 and the activity of protein kinases are further regulated by protein phosphatases. These data suggest that GluR1 phosphorylation of Ser831 and Ser845 via stimulation of group I mGluRs is regulated by the interactions of PLC-coupled protein kinases and protein phosphatases in the dorsal striatum. The American Society for Pharmacology and Experimental Therapeutics ER -