MECHANISM OF PROTEIN-KINASE-C ACTIVATION DURING THE INDUCTION AND MAINTENANCE OF LONG-TERM POTENTIATION PROBED USING A SELECTIVE PEPTIDE SUBSTRATE

被引:159
作者
KLANN, E
CHEN, SJ
SWEATT, JD
机构
[1] Division of Neuroscience, Baylor College of Medicine, Houston
关键词
HIPPOCAMPUS; SYNAPTIC PLASTICITY; PHOSPHORYLATION;
D O I
10.1073/pnas.90.18.8337
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Previous reports using various protein kinase inhibitors have suggested that protein kinase activity is necessary for both the induction and maintenance of hippocampal long-term potentiation (LTP), a cellular phenomenon likely to contribute to mammalian memory formation. We designed and characterized a selective peptide substrate for protein kinase C (PKC), corresponding to amino acids 28 to 43 of the neuronal protein neurogranin, and used the substrate to obtain direct biochemical evidence for activation of PKC in both the induction and maintenance phases of LTP. As the effect cannot be accounted for by either of two well-known mechanisms for persistent PKC activation, membrane insertion, or proteolysis, the persistent activation of PKC in the maintenance phase of LTP appears to occur via another mechanism. The maintenance phase of LTP is associated with decreased immunoreactivity of PKC, an effect that can be reversed with phosphatase treatment. Thus, PKC appears to be both phosphorylated and persistently activated in the maintenance phase of LTP.
引用
收藏
页码:8337 / 8341
页数:5
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