Editors' ChoiceSignaling Complexes

Tethered and Regulated

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Science's STKE  19 Jun 2001:
Vol. 2001, Issue 87, pp. tw1
DOI: 10.1126/stke.2001.87.tw1

Targeting proteins that localize kinases and other signaling molecules are clearly key components that promote interaction of appropriate molecules in signaling complexes. But such localization may be only one aspect of the regulation actually occurring on such targeting proteins. During generation of synaptic plasticity in hippocampal neurons (which is thought to represent a mechanism for learning and memory), the calcium- and calmodulin-dependent protein kinase II (CaMKII) translocates to N-methyl-D-aspartate (NMDA) receptor complexes and interacts directly with the NR2B subunit of the receptor. Bayer et al. report in vitro analysis of interaction of peptides from NR2B with CaMKII that show that the interaction of kinase and receptor subunit may have important effects on the activity of CaMKII. When interacting with the NR2B peptide, the kinase is activated by calcium and calmodulin (Ca2+/CM), but can remain autonomously active when the Ca2+/CM is removed, thus prolonging a Ca2+-induced activation of the enzyme. Ordinarily this behavior of the enzyme requires autophosphorylation, but the receptor-bound enzyme appears not to require this modification. One fragment of NR2B has sequence similarity to the autoinhibitory domain of the kinase and may thus impinge on the regulatory conformational changes in the enzyme.

K.-U. Bayer, P. De Koninck, A. S. Leonard, J. W. Hell, H. Schulman, Interaction with the NMDA receptor locks CaMKII in an active conformation. Nature 411, 801-805 (2001) [Online Journal]

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