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Science 19 February 1993: Vol. 259. no. 5098, pp. 1173 - 1175 DOI: 10.1126/science.8382377
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Articles
Science, Vol 259, Issue 5098, 1173-1175
Copyright © 1993 by American Association for the Advancement of Science
Phosphorylation and modulation of a kainate receptor (GluR6) by cAMP-dependent protein kinase
LY Wang,
FA Taverna,
XP Huang,
JF MacDonald,
and
DR Hampson
Department of Physiology, University of Toronto, Ontario, Canada.
Ligand-gated ion channels gated by glutamate constitute the major excitatory neurotransmitter system in the mammalian brain. The functional modulation of GluR6, a kainate-activated glutamate receptor, by adenosine 3',5'-monophosphate-dependent protein kinase A (PKA) was examined with receptors expressed in human embryonic kidney cells. Kainate-evoked currents underwent a rapid desensitization that was blocked by lectins. Kainate currents were potentiated by intracellular perfusion of PKA, and this potentiation was blocked by co-application of an inhibitory peptide. Site-directed mutagenesis was used to identify the site or sites of phosphorylation on GluR6. Although mutagenesis of two serine residues, Ser684 and Ser666, was required for complete abolition of the PKA-induced potentiation, Ser684 may be the preferred site of phosphorylation in native GluR6 receptor complexes. These results indicate that glutamate receptor function can be directly modulated by protein phosphorylation and suggest that a dynamic regulation of excitatory receptors could be associated with some forms of learning and memory in the mammalian brain.
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