Protected-site phosphorylation of protein kinase C in hippocampal long- term potentiation

J. David Sweatt, Coleen M Atkins, Joanne Johnson, Joey D. English, Erik D. Roberson, Shu Jen Chen, Alexandra Newton, Eric Klann

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

One important aspect of synaptic plasticity is that transient stimulation of neuronal cell surface receptors can lead to long-lasting biochemical and physiological effects in neurons. In long-term potentiation (LTP), generation of autonomously active protein kinase C (PKC) is one biochemical effect persisting beyond the NMDA receptor activation that triggers plasticity We previously observed that the expression of early LTP is associated with a phosphatase-reversible alteration in PKC immunoreactivity, suggesting that autophosphorylation of PKC might be elevated in LTP. In the present studies we tested the hypothesis that PKC phosphorylation is persistently increased in the early maintenance of LTP. We generated an antiserum that selectively recognizes the α and βII isoforms of PKC autophosphorylated in the C-terminal domain. Using western blotting with this antiserum we observed an NMDA receptor-mediated increase in phosphorylation of PKC 1 h after LTP was induced. How is the increased phosphorylation maintained in the cell in the face of ongoing phosphatase activity? We observed that dephosphorylation of PKC in vitro requires the presence of cofactors normally serving to activate PKC, i.e., Ca2+, phosphatidylserine, and diacylglycerol. Based on these observations and computer modeling of the three-dimensional structure of the PKC catalytic core, we propose a 'protected site' model of PKC autophosphorylation, whereby the conformation of PKC regulates accessibility of the phosphates to phosphatase. Although we have proposed the protected site model based on our studies of PKC phosphorylation in LTP, phosphorylation of protected sites might be a general biochemical mechanism for the generation of stable, long- lasting physiologic changes.

Original languageEnglish
Pages (from-to)1075-1085
Number of pages11
JournalJournal of Neurochemistry
Volume71
Issue number3
StatePublished - Sep 1 1998
Externally publishedYes

Fingerprint

Phosphorylation
Long-Term Potentiation
Protein Kinase C
Phosphoric Monoester Hydrolases
N-Methyl-D-Aspartate Receptors
Plasticity
Immune Sera
Neuronal Plasticity
Phosphatidylserines
Diglycerides
Cell Surface Receptors
Neurons
Conformations
Catalytic Domain
Protein Isoforms
Western Blotting
Chemical activation
Phosphates
Maintenance

Keywords

  • Autophosphorylation
  • Dephosphorylation
  • Hippocampus
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Sweatt, J. D., Atkins, C. M., Johnson, J., English, J. D., Roberson, E. D., Chen, S. J., ... Klann, E. (1998). Protected-site phosphorylation of protein kinase C in hippocampal long- term potentiation. Journal of Neurochemistry, 71(3), 1075-1085.

Protected-site phosphorylation of protein kinase C in hippocampal long- term potentiation. / Sweatt, J. David; Atkins, Coleen M; Johnson, Joanne; English, Joey D.; Roberson, Erik D.; Chen, Shu Jen; Newton, Alexandra; Klann, Eric.

In: Journal of Neurochemistry, Vol. 71, No. 3, 01.09.1998, p. 1075-1085.

Research output: Contribution to journalArticle

Sweatt, JD, Atkins, CM, Johnson, J, English, JD, Roberson, ED, Chen, SJ, Newton, A & Klann, E 1998, 'Protected-site phosphorylation of protein kinase C in hippocampal long- term potentiation', Journal of Neurochemistry, vol. 71, no. 3, pp. 1075-1085.
Sweatt JD, Atkins CM, Johnson J, English JD, Roberson ED, Chen SJ et al. Protected-site phosphorylation of protein kinase C in hippocampal long- term potentiation. Journal of Neurochemistry. 1998 Sep 1;71(3):1075-1085.
Sweatt, J. David ; Atkins, Coleen M ; Johnson, Joanne ; English, Joey D. ; Roberson, Erik D. ; Chen, Shu Jen ; Newton, Alexandra ; Klann, Eric. / Protected-site phosphorylation of protein kinase C in hippocampal long- term potentiation. In: Journal of Neurochemistry. 1998 ; Vol. 71, No. 3. pp. 1075-1085.
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