IDENTIFICATION OF A CA2-DEPENDENT PROTEIN-KINASE-II REGULATORY PHOSPHORYLATION SITE IN NON-N-METHYL-D-ASPARTATE GLUTAMATE RECEPTORS( CALMODULIN)

Glutamate receptor ion channels are colocalized in postsynaptic densit ies with Ca2+/calmodulin-dependent protein kinase II (CaM-kinase II), which can phosphorylate and strongly enhance non-N-methyl-D-aspartate (NMDA) glutamate receptor current. In this study, CaM-kinase LI enhanc ed kainate currents of expressed glutamate receptor 6 in 293 cells and of wild-type glutamate receptor 1, but not the Ser-627 to Ala mutant, in Xenopus oocytes. A synthetic peptide corresponding to residues 620 -638 in GluR1 was phosphorylated in vitro by CaM-kinase II but not by cAMP-dependent protein kinase or protein kinase C. The P-32-labeled pe ptide map of this synthetic peptide appears to be the same as the two- dimensional peptide map of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (Ah IPA) glutamate receptors phosphorylated in cultured hip pocampal neurons by CaM-kinase II described elsewhere. This CaM-kinase II regulatory phosphorylation site is conserved in all AMPA/kainate-t ype glutamate receptors, and its phosphorylation may be important in e nhancing postsynaptic responsiveness as occurs during synaptic plastic ity.