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Dose Response
2010 Jan 29;83:347-67. doi: 10.2203/dose-response.09-017.Luke.
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Employing a Mechanistic Model for the MAPK Pathway to Examine the Impact of Cellular all or None Behavior on Overall Tissue Response.
Luke NS
,
Devito MJ
,
Portier CJ
,
El-Masri HA
.
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The mitogen activated protein kinase (MAPK) cascade is a three-tiered phosphorylation cascade that is ubiquitously expressed among eukaryotic cells. Its primary function is to propagate signals from cell surface receptors to various cytosolic and nuclear targets. Recent studies have demonstrated that the MAPK cascade exhibits an all-or-none response to graded stimuli. This study quantitatively investigates MAPK activation in Xenopus oocytes using both empirical and biologically-based mechanistic models. Empirical models can represent overall tissue MAPK activation in the oocytes. However, these models lack description of key biological processes and therefore give no insight into whether the cellular response occurs in a graded or all-or-none fashion. To examine the propagation of cellular MAPK all-or-none activation to overall tissue response, mechanistic models in conjunction with Monte Carlo simulations are employed. An adequate description of the dose response relationship of MAPK activation in Xenopus oocytes is achieved. Furthermore, application of these mechanistic models revealed that the initial receptor-ligand binding rate contributes to the cells' ability to exhibit an all-or-none MAPK activation response, while downstream activation parameters contribute more to the magnitude of activation. These mechanistic models enable us to identify key biological events which quantitatively impact the shape of the dose response curve, especially at low environmentally relevant doses.
Andersen,
The use of quantitative histological and molecular data for risk assessment and biologically based model development.
2002, Pubmed
Andersen,
The use of quantitative histological and molecular data for risk assessment and biologically based model development.
2002,
Pubmed
Andersen,
Molecular circuits, biological switches, and nonlinear dose-response relationships.
2002,
Pubmed
Apáti,
Calcium induces cell survival and proliferation through the activation of the MAPK pathway in a human hormone-dependent leukemia cell line, TF-1.
2003,
Pubmed
Bagowski,
Bistability in the JNK cascade.
2001,
Pubmed
,
Xenbase
Bhalla,
MAP kinase phosphatase as a locus of flexibility in a mitogen-activated protein kinase signaling network.
2002,
Pubmed
Bühler,
Zonation of cytochrome P450 isozyme expression and induction in rat liver.
1992,
Pubmed
Chickarmane,
Oscillatory dynamics arising from competitive inhibition and multisite phosphorylation.
2007,
Pubmed
Cooper,
Roles of mitogen activated protein kinases and EGF receptor in arsenite-stimulated matrix metalloproteinase-9 production.
2004,
Pubmed
Cuthbertson,
Modelling receptor-controlled intracellular calcium oscillators.
1991,
Pubmed
Dong,
The molecular mechanisms of arsenic-induced cell transformation and apoptosis.
2002,
Pubmed
El-Masri,
Replication potential of cells via the protein kinase C-MAPK pathway: application of a mathematical model.
1999,
Pubmed
Ferrell,
The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Fox,
Gene expression and cell proliferation in rat liver after 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.
1993,
Pubmed
Hoel,
Implication of nonlinear kinetics on risk estimation in carcinogenesis.
1983,
Pubmed
Kholodenko,
Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades.
2000,
Pubmed
Kholodenko,
Untangling the signalling wires.
2007,
Pubmed
Kolch,
When kinases meet mathematics: the systems biology of MAPK signalling.
2005,
Pubmed
Lewis,
Signal transduction through MAP kinase cascades.
1998,
Pubmed
Mackeigan,
Graded mitogen-activated protein kinase activity precedes switch-like c-Fos induction in mammalian cells.
2005,
Pubmed
,
Xenbase
Markevich,
Long-range signaling by phosphoprotein waves arising from bistability in protein kinase cascades.
2006,
Pubmed
Markevich,
Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades.
2004,
Pubmed
Mattie,
Copper-inducible transcription: regulation by metal- and oxidative stress-responsive pathways.
2004,
Pubmed
Mossman,
Oxidants and signaling by mitogen-activated protein kinases in lung epithelium.
2006,
Pubmed
Mutalik,
Effect of the MAPK cascade structure, nuclear translocation and regulation of transcription factors on gene expression.
2006,
Pubmed
Neti,
Log normal distribution of cellular uptake of radioactivity: implications for biologic responses to radiopharmaceuticals.
2006,
Pubmed
Ortega,
Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements.
2006,
Pubmed
Orton,
Computational modelling of the receptor-tyrosine-kinase-activated MAPK pathway.
2005,
Pubmed
Owuor,
Antioxidants and oxidants regulated signal transduction pathways.
2002,
Pubmed
Pirone,
Fluctuations in transcription factor binding can explain the graded and binary responses observed in inducible gene expression.
2004,
Pubmed
Ramos-Nino,
Role of mitogen-activated protein kinases (MAPK) in cell injury and proliferation by environmental particulates.
2002,
Pubmed
Salazar,
Kinetic models of phosphorylation cycles: a systematic approach using the rapid-equilibrium approximation for protein-protein interactions.
2006,
Pubmed
Schwacke,
The potential for signal integration and processing in interacting MAP kinase cascades.
2007,
Pubmed
Shaulian,
AP-1 in cell proliferation and survival.
2001,
Pubmed
Sheiner,
Pharmacokinetic parameter estimates from several least squares procedures: superiority of extended least squares.
1985,
Pubmed
Tai,
Adenosine triphosphate activates mitogen-activated protein kinase in human granulosa-luteal cells.
2001,
Pubmed
Tritscher,
Dose-response relationships for chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in a rat tumor promotion model: quantification and immunolocalization of CYP1A1 and CYP1A2 in the liver.
1992,
Pubmed
Vayttaden,
A spectrum of models of signaling pathways.
2004,
Pubmed
Widmann,
Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human.
1999,
Pubmed
Yamaguchi,
The protein kinase C isoforms leading to MAP-kinase activation in CHO cells.
1995,
Pubmed
Zhang,
Binary gene induction and protein expression in individual cells.
2006,
Pubmed
Zhong,
MAPK/AP-1 signal pathway in tobacco smoke-induced cell proliferation and squamous metaplasia in the lungs of rats.
2005,
Pubmed
