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Transient Versus Asymptotic Dynamics of CaM Kinase II: Possible Roles of Phosphatase

Kubota, Yoshihisa and Bower, James M. (2001) Transient Versus Asymptotic Dynamics of CaM Kinase II: Possible Roles of Phosphatase. Journal of Computational Neuroscience, 11 (3). pp. 263-279. ISSN 0929-5313. https://resolver.caltech.edu/CaltechAUTHORS:20191112-103201813

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Abstract

Calmodulin-dependent protein kinase II (CaMKII) is known to play a key role during induction of long-term potentiation (LTP). Given the dependence of LTP on the frequency of synaptic activation, several previous modeling efforts have proposed that biochemical properties of CaMKII itself might be in part responsible for this dependence. Recently, De Koninck and Schulman (1998) have provided direct experimental evidence that the enzyme itself is sensitive to the frequency of Ca²⁺ activation. Here we demonstrate the ability of a detailed biophysical model constructed solely on enzyme kinetics of purified proteins to generate the frequency sensitivity demonstrated by De Koninck and Schulman. Quantitative analysis of the model reveals that this frequency sensitivity is provided by a mechanism different from those previously postulated. This analysis leads to specific predictions concerning the effects of mutations on this process. We further employ the model to examine the asymptotic behavior of CaMKII-phosphatase system during longer simulated periods of stimulation. The analyses of the model suggest that the transient and asymptotic frequency sensitivity of this enzyme are dependent on different biochemical mechanisms. These results may be applicable to Ca²⁺/calmodulin signaling pathways in general.


Item Type:Article
Related URLs:
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https://doi.org/10.1023/a:1013727331979DOIArticle
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Additional Information:© 2001 Kluwer Academic Publishers. Received January 3, 2001; Revised October 12, 2001; Accepted October 16, 2001. We thank Howard Schulman for communicating unpublished data and for insightful comments on the manuscripts; Paul De Koninck, Mike Bradshaw, and Ulrich K. Bayer (Department of Neurobiology, Stanford University School of Medicine) and Sachiko Murase (Division of Biology, California Institute of Technology) for valuable discussions and/or comments on the manuscript. Travel support was provided by the Exploratory Research for Advanced Technology, (ERATO) Kitano Project to Y.K. Support for J.M.B. was provided by a grant from the Multidisciplinary Research Program of the University Research Initiative (MURI) of the Army Research Office (ARO).
Funders:
Funding AgencyGrant Number
Exploratory Research for Advanced Technology (ERATO)UNSPECIFIED
Army Research Office (ARO)UNSPECIFIED
Subject Keywords:CaM kinase II; protein phosphatase 1; frequency sensitivity; transient dynamics; computational enzymology
Issue or Number:3
Record Number:CaltechAUTHORS:20191112-103201813
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20191112-103201813
Official Citation:Kubota, Y. & Bower, J.M. J Comput Neurosci (2001) 11: 263. https://doi.org/10.1023/A:1013727331979
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:99805
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:12 Nov 2019 22:58
Last Modified:12 Nov 2019 22:58

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