TY - JOUR
T1 - Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the α-amino-3-hydroxyl-5-methyl-4- isoxazole-propionate-type glutamate receptor
AU - Barria, Andres
AU - Derkach, Victor
AU - Soderling, Thomas
PY - 1997/12/26
Y1 - 1997/12/26
N2 - Ca2+/CaM-dependent protein kinase II (CaM-KII) can phosphorylate and potentiate responses of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate- type glutamate receptors in a number of systems, and recent studies implicate this mechanism in long term potentiation, a cellular model of learning and memory. In this study we have identified this CaM-KII regulatory site using deletion and site-specific mutants of glutamate receptor 1 (GIuR1). Only mutations affecting Set831 altered the 32P peptide maps of GluR1 from HEK-293 cells co- expressing an activated CaM-KII. Likewise, when CaM-KII was infused into cells expressing GluR1, the Ser831 to Ala mutant failed to show potentiation of the GluR1 current. The Ser831 site is specific to GluR1, and CaM-KII did not phosphorylate or potentiate current in cells expressing GluR2, emphasizing the importance of the GluR1 subunit in this regulatory mechanism. Because Set831 has previously been identified as a protein kinase C phosphorylation site (Roche. K. W., O'Brien, R. J., Mammen, A. L., Bernhardt, J., and Huganir, R. L. (1996) Neuron 16, 1179-1188), this raises the possibility of synergistic interactions between CaM-KII and protein kinase C in regulating synaptic plasticity.
AB - Ca2+/CaM-dependent protein kinase II (CaM-KII) can phosphorylate and potentiate responses of α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate- type glutamate receptors in a number of systems, and recent studies implicate this mechanism in long term potentiation, a cellular model of learning and memory. In this study we have identified this CaM-KII regulatory site using deletion and site-specific mutants of glutamate receptor 1 (GIuR1). Only mutations affecting Set831 altered the 32P peptide maps of GluR1 from HEK-293 cells co- expressing an activated CaM-KII. Likewise, when CaM-KII was infused into cells expressing GluR1, the Ser831 to Ala mutant failed to show potentiation of the GluR1 current. The Ser831 site is specific to GluR1, and CaM-KII did not phosphorylate or potentiate current in cells expressing GluR2, emphasizing the importance of the GluR1 subunit in this regulatory mechanism. Because Set831 has previously been identified as a protein kinase C phosphorylation site (Roche. K. W., O'Brien, R. J., Mammen, A. L., Bernhardt, J., and Huganir, R. L. (1996) Neuron 16, 1179-1188), this raises the possibility of synergistic interactions between CaM-KII and protein kinase C in regulating synaptic plasticity.
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U2 - 10.1074/jbc.272.52.32727
DO - 10.1074/jbc.272.52.32727
M3 - Article
C2 - 9407043
AN - SCOPUS:0031283172
SN - 0021-9258
VL - 272
SP - 32727
EP - 32730
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 52
ER -