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Science 6 February 1998:
Vol. 279. no. 5352, pp. 870 - 873
DOI: 10.1126/science.279.5352.870
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Reports

Autophosphorylation at Thr286 of the alpha  Calcium-Calmodulin Kinase II in LTP and Learning

Karl Peter Giese, Nikolai B. Fedorov, Robert K. Filipkowski, Alcino J. Silva *

The calcium-calmodulin-dependent kinase II (CaMKII) is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, CaMKII can undergo autophosphorylation, resulting in CaM-independent activity. A point mutation was introduced into the alpha CaMKII gene that blocked the autophosphorylation of threonine at position 286 (Thr286) of this kinase without affecting its CaM-dependent activity. The mutant mice had no N-methyl-D-aspartate receptor-dependent LTP in the hippocampal CA1 area and showed no spatial learning in the Morris water maze. Thus, the autophosphorylation of alpha CaMKII at Thr286 appears to be required for LTP and learning.

K. P. Giese, N. B. Fedorov, A. J. Silva, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
R. K. Filipkowski, Department of Neurophysiology, Nencki Institute, PL-02-093 Warsaw, Poland.
*   To whom correspondence should be addressed.

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Adult Learning Deficits after Neonatal Exposure to D-Methamphetamine: Selective Effects on Spatial Navigation and Memory.
C. V. Vorhees, S. L. Inman-Wood, L. L. Morford, H. W. Broening, M. Fukumura, and M. S. Moran (2000)
J. Neurosci. 20, 4732-4739
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Three-dimensional Reconstructions of Calcium/Calmodulin-dependent (CaM) Kinase IIalpha and Truncated CaM Kinase IIalpha Reveal a Unique Organization for Its Structural Core and Functional Domains.
S. J. Kolodziej, A. Hudmon, M. N. Waxham, and J. K. Stoops (2000)
J. Biol. Chem. 275, 14354-14359
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Calmodulin-Binding Peptide PEP-19 Modulates Activation of Calmodulin Kinase