Advertisement

Biological Cybernetics

, Volume 82, Issue 1, pp 35–47 | Cite as

Switching characteristics of a model for biochemical-reaction networks describing autophosphorylation versus dephosphorylation of Ca2+/calmodulin-dependent protein kinase II

  • Hiroshi Okamoto
  • Kazuhisa Ichikawa
Article

Abstract.

Ca2+/calmodulin-dependent protein kinase II (CaMKII) has been suggested to participate in various cellular phenomena triggered by Ca2+ signalling. In the present study, we addressed the functional role of CaMKII in molecular-signal transduction in cells by mathematical modelling of putative biochemical-reaction networks thought to represent an essential part of molecular events responsible for CaMKII-related cellular phenomena. These networks include Ca2+/calmodulin-dependent threonine-286/287 (Thr286/287) autophosphorylation of CaMKII versus dephosphorylation of the enzyme. Computer simulation of the model was performed to examine the relation between the Ca2+-signalling pattern as an input and the resulting degree of Thr286/287 autophosphorylation (m) as an output. Under the simplified condition that the Ca2+ concentration during Ca2+ signalling was set to remain constant with time, the biochemical-reaction networks were shown to function as a switch. There is a threshold for γ, a parameter representing the probability that the Thr286/287-dephosphorylated CaMKII subunit binds with the Ca2+/calmodulin complex; if γ is above this threshold, m increases with time to a large degree (switch-on); otherwise, it remains near zero (switch-off). Mathematically, this sharp onset of m at the threshold can be accounted for by a change in the structure of the dynamic system describing the model, from bistability to monostability; this is analogous to the first-order phase transition in statistical physics. For the oscillatory time course of [Ca2+], switching characteristics were also shown with respect to the frequency and the maximum amplitude of the oscillation. These results suggest that graded information mediated by Ca2+ signalling is digitized into all-or-non information mediated by Thr286/287 autophosphorylation of CaMKII.

Keywords

Enzyme Phase Transition Dynamic System Protein Kinase Computer Simulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • Hiroshi Okamoto
    • 1
  • Kazuhisa Ichikawa
    • 1
  1. 1.Corporate Research Labs, Fuji Xerox Co., Ltd. 430 Sakai, Nakai-machi, Ashigarakami-gun, Kanagawa 259-0157, JapanJP

Personalised recommendations