1 research outputs found
Regulation of signal duration and the statistical dynamics of kinase activation by scaffold proteins
Scaffolding proteins that direct the assembly of multiple kinases into a
spatially localized signaling complex are often essential for the maintenance
of an appropriate biological response. Although scaffolds are widely believed
to have dramatic effects on the dynamics of signal propagation, the mechanisms
that underlie these consequences are not well understood. Here, Monte Carlo
simulations of a model kinase cascade are used to investigate how the temporal
characteristics of signaling cascades can be influenced by the presence of
scaffold proteins. Specifically, we examine the effects of spatially localizing
kinase components on a scaffold on signaling dynamics. The simulations indicate
that a major effect that scaffolds exert on the dynamics of cell signaling is
to control how the activation of protein kinases is distributed over time.
Scaffolds can influence the timing of kinase activation by allowing for kinases
to become activated over a broad range of times, thus allowing for signaling at
both early and late times. Scaffold concentrations that result in optimal
signal amplitude also result in the broadest distributions of times over which
kinases are activated. These calculations provide insights into one mechanism
that describes how the duration of a signal can potentially be regulated in a
scaffold mediated protein kinase cascade. Our results illustrate another
complexity in the broad array of control properties that emerge from the
physical effects of spatially localizing components of kinase cascades on
scaffold proteins.Comment: 12 pages, 6 figure