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Abstract:

Mitogen-activated protein kinase (MAPK) signaling pathways play an essential role in the transduction of environmental stimuli to the nucleus, thereby regulating a variety of cellular processes, including cell proliferation, differentiation and programmed cell death. The components of the MAPK extracellular activated protein kinase (ERK) cascade represent attractive targets for cancer therapy as their aberrant activation is a frequent event among highly prevalent human cancers. MAPK networks are a model for computational simulation, mostly using ordinary and partial differential equations. Key results showed that these networks can have switch-like behavior, bistability and oscillations. In this work, we consider three representative ERK networks, one with a negative feedback loop, which present a binomial steady state ideal under mass-action kinetics. We therefore apply the theoretical result present in [27] to find a set of rate constants that allow two significantly different stable steady states in the same stoichiometric compatibility class for each network. Our approach makes it possible to study certain aspects of the system, such as multistationarity, without relying on simulation, since we do not assume a priori any constant but the topology of the network. As the performed analysis is general it could be applied to many other important biochemical networks. © 2015 Elsevier Inc.

Registro:

Documento: Artículo
Título:MAPK's networks and their capacity for multistationarity due to toric steady states
Autor:Pérez Millán, M.; Turjanski, A.G.
Filiación:Dto. de Matemática, FCEN, Universidad de Buenos Aires, Ciudad Universitaria, Pab. I, C1428EGABuenos Aires, Argentina
Dto. de Ciencias Exactas, CBC, Universidad de Buenos Aires, Ramos Mejía 841, C1405CAE, Buenos Aires, Argentina
Dto. de Química Biológica, FCEN, Universidad de Buenos Aires, Ciudad Universitaria, Pab. II, C1428EGA, Buenos Aires, Argentina
Palabras clave:MAPK; Mass-action kinetics; Multistationarity; Signaling networks; Toric steady states; Cell death; Cell proliferation; Cell signaling; Differential equations; Diseases; Enzyme activity; Enzymes; Feedback; Mobile security; Ordinary differential equations; Proteins; Rate constants; Signaling; MAPK; Mass action kinetics; Multistationarity; Signaling networks; Steady state; Switching circuits; mitogen activated protein kinase; phosphatase; Raf protein; biochemistry; biological analysis; cancer; cell organelle; computer simulation; enzyme activity; protein; Article; binomial distribution; controlled study; enzyme activation; enzyme activity; enzyme chemistry; mass action; mathematical computing; negative feedback; signal transduction; steady state; stoichiometry; system analysis; theoretical study; toric steady state; biological model; feedback system; human; kinetics; mathematical phenomena; Feedback, Physiological; Humans; Kinetics; MAP Kinase Signaling System; Mathematical Concepts; Models, Biological
Año:2015
Volumen:262
Página de inicio:125
Página de fin:137
DOI: http://dx.doi.org/10.1016/j.mbs.2014.12.010
Título revista:Mathematical Biosciences
Título revista abreviado:Math. Biosci.
ISSN:00255564
CODEN:MABIA
CAS:mitogen activated protein kinase, 142243-02-5; phosphatase, 9013-05-2
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00255564_v262_n_p125_PerezMillan

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Citas:

---------- APA ----------
Pérez Millán, M. & Turjanski, A.G. (2015) . MAPK's networks and their capacity for multistationarity due to toric steady states. Mathematical Biosciences, 262, 125-137.
http://dx.doi.org/10.1016/j.mbs.2014.12.010
---------- CHICAGO ----------
Pérez Millán, M., Turjanski, A.G. "MAPK's networks and their capacity for multistationarity due to toric steady states" . Mathematical Biosciences 262 (2015) : 125-137.
http://dx.doi.org/10.1016/j.mbs.2014.12.010
---------- MLA ----------
Pérez Millán, M., Turjanski, A.G. "MAPK's networks and their capacity for multistationarity due to toric steady states" . Mathematical Biosciences, vol. 262, 2015, pp. 125-137.
http://dx.doi.org/10.1016/j.mbs.2014.12.010
---------- VANCOUVER ----------
Pérez Millán, M., Turjanski, A.G. MAPK's networks and their capacity for multistationarity due to toric steady states. Math. Biosci. 2015;262:125-137.
http://dx.doi.org/10.1016/j.mbs.2014.12.010