Department of Anesthesiology

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Specificity of protein kinase inhibitor peptides and induction of long-term potentiation.

TitleSpecificity of protein kinase inhibitor peptides and induction of long-term potentiation.
Publication TypeJournal Article
Year of Publication1994
AuthorsHvalby O, Hemmings HC, Paulsen O, Czernik AJ, Nairn AC, Godfraind JM, Jensen V, Raastad M, Storm JF, Andersen P
JournalProc Natl Acad Sci U S A
Volume91
Issue11
Pagination4761-5
Date Published1994 May 24
ISSN0027-8424
KeywordsAmino Acid Sequence, Animals, Calcium-Calmodulin-Dependent Protein Kinases, Long-Term Potentiation, Male, Molecular Sequence Data, Peptides, Protein Kinase C, Pyramidal Cells, Rats, Rats, Wistar, Substrate Specificity
Abstract

Previous studies have used synthetic peptide analogs, corresponding to sequences within the pseudosubstrate domain of protein kinase C (PKC) or the autoregulatory domain of Ca2+/calmodulin-dependent protein kinase II (CaMKII), in attempts to define the contribution of each of these protein kinases to induction of long-term potentiation (LTP). However, the specificity of these inhibitor peptides is not absolute. Using intracellular delivery to rat CA1 hippocampal neurons, we have determined the relative potency of two protein kinase inhibitor peptides, PKC-(19-36) and [Ala286]CaMKII-(281-302), as inhibitors of the induction of LTP. Both peptides blocked the induction of LTP; however, PKC-(19-36) was 30-fold more potent than [Ala286]CaMKII-(281-302). The relative specificity of PKC-(19-36), [Ala286]CaMKII-(281-302), and several other CaMKII peptide analogs for protein kinase inhibition in vitro was also determined. A comparison of the potencies of PKC-(19-36) and [Ala286]CaMKII-(281-302) in the physiological assay with their Ki values for protein kinase inhibition in vitro indicates that the blockade of induction of LTP observed for each peptide is attributable to inhibition of PKC.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID8197132
PubMed Central IDPMC43868
Grant ListMH 39327 / MH / NIMH NIH HHS / United States