n-site phosphorylation systems with 2n-1 steady states

DOI10.1007/S11538-014-9984-0MaRDI QIDQ467732zbMATH OpenOpenAlexWikidataFDO

Authors D. Flockerzi, Katharina Holstein, Carsten Conradi

Publication date 5 November 2014

Published in Bulletin of Mathematical Biology (Search for Journal in Brave)

Full work available at URL https://arxiv.org/abs/1312.4774

zbMATH Keywords

determining equationmass-action kineticsmultistationaritysequential-distributed phosphorylation

Mathematics Subject Classification ID

Biochemistry, molecular biology (92C40) Cell biology (92C37)

Abstract: Multisite protein phosphorylation plays a prominent role in intracellular processes like signal transduction, cell-cycle control and nuclear signal integration. Many proteins are phosphorylated in a sequential and distributive way at more than one phosphorylation site. Mathematical models of $n$-site sequential distributive phosphorylation are therefore studied frequently. In particular, in {em Wang and Sontag, 2008,} it is shown that models of $n$-site sequential distributive phosphorylation admit at most $2n-1$ steady states. Wang and Sontag furthermore conjecture that for odd $n$, there are at most $n$ and that, for even $n$, there are at most $n+1$ steady states. This, however, is not true: building on earlier work in {em Holstein et.al., 2013}, we present a scalar determining equation for multistationarity which will lead to parameter values where a $3$-site system has $5$ steady states and parameter values where a $4$-site system has $7$ steady states. Our results therefore are counterexamples to the conjecture of Wang and Sontag. We furthermore study the inherent geometric properties of multistationarity in $n$-site sequential distributive phosphorylation: the complete vector of steady state ratios is determined by the steady state ratios of free enzymes and unphosphorylated protein and there exists a linear relationship between steady state ratios of phosphorylated protein.

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Cites work

• Chemical reaction systems with toric steady states
• Complex-linear invariants of biochemical networks
• Multistationarity in mass action networks with applications to ERK activation
• Multistationarity in sequential distributed multisite phosphorylation networks
• Multistationarity in the activation of a MAPK: parametrizing the relevant region in parameter space
• Multistationarity, the basis of cell differentiation and memory. I: Structural conditions of multistationarity and other nontrivial behavior
• Multistationarity, the basis of cell differentiation and memory. II: Logical analysis of regulatory networks in terms of feedback circuits
• On the number of steady states in a multiple futile cycle
• The rational parameterisation theorem for multisite post-translational modification systems
• Ultrasensitivity in independent multisite systems

Cited in

(17)

• The steady-state degree and mixed volume of a chemical reaction network
• A global convergence result for processive multisite phosphorylation systems
• Multistationarity in the space of total concentrations for systems that admit a monomial parametrization
• Parameter regions that give rise to \(2\lfloor \frac{n}{2} \rfloor +1\) positive steady states in the \(n\)-site phosphorylation system
• An all-encompassing global convergence result for processive multisite phosphorylation systems
• The kinetic space of multistationarity in dual phosphorylation
• Families of toric chemical reaction networks
• Autophosphorylation and the dynamics of the activation of Lck
• Parameter Region for Multistationarity in \({\boldsymbol{n-}}\)Site Phosphorylation Networks
• On the existence of Hopf bifurcations in the sequential and distributive double phosphorylation cycle
• Introduction to the geometric theory of ODEs with applications to chemical processes
• A proof of bistability for the dual futile cycle
• On the number of steady states in a multiple futile cycle
• Geometry of the signed support of a multivariate polynomial and Descartes' rule of signs
• Implicit dose-response curves
• Multistationarity in sequential distributed multisite phosphorylation networks
• A proof of unlimited multistability for phosphorylation cycles

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