Abstract:
In biochemical signaling pathways without explicit feedback connections, the core signal transduction is usually described as a one-way communication, going from upstream to downstream in a feedforward chain or network of covalent modification cycles. In this paper we explore the possibility of a new type of signaling called retroactive signaling, offered by the recently demonstrated property of retroactivity in signaling cascades. The possibility of retroactive signaling is analysed in the simplest case of the stationary states of a bicyclic cascade of signaling cycles. In this case, we work out the conditions for which variables of the upstream cycle are affected by a change of the total amount of protein in the downstream cycle, or by a variation of the phosphatase deactivating the same protein. Particularly, we predict the characteristic ranges of the downstream protein, or of the downstream phosphatase, for which a retroactive effect can be observed on the upstream cycle variables. Next, we extend the possibility of retroactive signaling in short but nonlinear signaling pathways involving a few covalent modification cycles. © 2012 Sepulchre et al.
Registro:
Documento: |
Artículo
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Título: | Retroactive signaling in short signaling pathways |
Autor: | Sepulchre, J.-A.; Merajver, S.D.; Ventura, A.C. |
Filiación: | Institut Non Linéaire de Nice, UMR 7335 CNRS - University of Nice Sophia Antipolis, Valbonne, France Department of Internal Medicine, and Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, United States Instituto de Fisiología, Biología Molecular y Neurociencias, CONICET and Departamento de Fisiología, Biología Molecular y Celular, Universidad de Buenos Aires, Buenos Aires, Argentina
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Palabras clave: | phosphatase; article; enzyme inactivation; intracellular signaling; negative feedback; positive feedback; protein analysis; protein modification; retroactive signaling; signal transduction; Enzyme Activation; Models, Biological; Phosphoprotein Phosphatases; Signal Transduction |
Año: | 2012
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Volumen: | 7
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Número: | 7
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DOI: |
http://dx.doi.org/10.1371/journal.pone.0040806 |
Título revista: | PLoS ONE
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Título revista abreviado: | PLoS ONE
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ISSN: | 19326203
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CAS: | phosphatase, 9013-05-2; Phosphoprotein Phosphatases, 3.1.3.16
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19326203_v7_n7_p_Sepulchre |
Referencias:
- Nelson, D., Cox, M., (2004) Lehninger Principles of Biochemistry, p. 1100. , Fourth Edition, W. H. Freeman
- Seger, R., Krebs, E.G., The mapk signaling cascade (1995) FASEB J, 9, pp. 726-735
- Huang, C.Y., Ferrell, J.E., Ultrasensitivity in the mitogen-activated protein kinase cascade (1996) Proc Natl Acad Sci U S A, 93, pp. 10078-10083
- Elion, E.A., Qi, M., Chen, W., Signal transduction. signaling specificity in yeast (2005) Science, 307, pp. 687-688
- Goldbeter, A., Koshland, J.D.E., An amplified sensitivity arising from covalent modification in biological systems (1981) Proc Natl Acad Sci U S A, 78, pp. 6840-6844
- Qiao, L., Nachbar, R.B., Kevrekidis, I.G., Shvartsman, S.Y., Bistability and oscillations in the huang-ferrell model of mapk signaling (2007) PLoS Comput Biol, 3, pp. 1819-1826
- Feliu, E., Knusden, M., Andersen, L., Wiuf, C., An algebraic approach to signaling cascades with n layers (2012) Bull Math Biol, 74, pp. 45-72
- Ventura, A.C., Sepulchre, J.A., Merajver, S.D., A hidden feedback in signaling cascades is revealed (2008) PLoS Comput Biol, 4, pp. e1000041
- Del Vecchio, D., Ninfa, A.J., Sontag, E.D., Modular cell biology: retroactivity and insulation (2008) Mol Syst Biol, 4, p. 161
- Ossareh, H.R., Ventura, A.C., Merajver, S.D., Del Vecchio, D., Long signaling cascades tend to attenuate retroactivity (2011) Biophys J, 100, pp. 1617-1626
- Andrianantoandro, E., Basu, S., Karig, D.K., Weiss, R., Synthetic biology: new engineering rules for an emerging discipline (2006) Mol Syst Biol, 2, pp. 0028-2006
- Franco, E., Del Vecchio, D., Murray, R., Design of insulating devices for in vitro synthetic circuits (2009) Proceedings of the IEEE Conference on Decision and Control, Shangai, pp. 4584-4589
- Anderson, J., Chang, Y., Papachristodoulou, A., Model decomposition and reduction tools for large-scale networks in systems biology (2011) Automatica, 47, pp. 1165-1174
- Hartwell, L.H., Hopfield, J.J., Leibler, S., Murray, A.W., From molecular to modular cell biology (1999) Nature, 402, pp. C47-C52
- Alexander, R.P., Kim, P.M., Emonet, T., Gerstein, M.B., Understanding modularity in molecular networks requires dynamics (2009) Sci Signal, 2, pp. pe44
- Wynn, M., Ventura, A., Sepulchre, J.A., Garca, H., Merajver, S., Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity (2011) BMC Systems Biology, 5, p. 156
- Kim, Y., Paroush, Z., Nairz, K., Hafen, E., Jimenez, G., Substrate-dependent control of mapk phosphorylation in vivo (2011) Mol Syst Biol, 7, p. 467
- Ventura, A.C., Jiang, P., van Wassenhove, L., Del Vecchio, D., Merajver, S.D., Signaling properties of a covalent modification cycle are altered by a downstream target (2010) Proc Natl Acad Sci U S A, 107, pp. 10032-10037
- Kim, Y., Coppey, M., Grossman, R., Ajuria, L., Jimenez, G., Mapk substrate competition integrates patterning signals in the drosophila embryo (2010) Curr Biol, 20, pp. 446-451
- Goldbeter, A., A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase (1991) Proc Natl Acad Sci U S A, 88, pp. 9107-9111
- Callis, J., Vierstra, R.D., Protein degradation in signaling (2000) Curr Opin Plant Biol, 3, pp. 381-386
- Soyer, O.S., Kuwahara, H., Csikasz-Nagy, A., Regulating the total level of a signaling protein can vary its dynamics in a range from switch like ultrasensitivity to adaptive responses (2009) FEBS J, 276, pp. 3290-3298
- Kumar, N., Afeyan, R., Kim, H.D., Lauffenburger, D.A., Multipathway model enables prediction of kinase inhibitor cross-talk effects on migration of her2-overexpressing mammary epithelial cells (2008) Mol Pharmacol, 73, pp. 1668-1678
- Jiang, P., Ventura, A.C., Sontag, E.D., Merajver, S.D., Ninfa, A.J., Load-induced modulation of signal transduction networks (2011) Sci Signal, 4
- Zumsande, M., Gross, T., Bifurcations and chaos in the mapk signaling cascade (2010) J of Theor Biol, 265, pp. 481-491
Citas:
---------- APA ----------
Sepulchre, J.-A., Merajver, S.D. & Ventura, A.C.
(2012)
. Retroactive signaling in short signaling pathways. PLoS ONE, 7(7).
http://dx.doi.org/10.1371/journal.pone.0040806---------- CHICAGO ----------
Sepulchre, J.-A., Merajver, S.D., Ventura, A.C.
"Retroactive signaling in short signaling pathways"
. PLoS ONE 7, no. 7
(2012).
http://dx.doi.org/10.1371/journal.pone.0040806---------- MLA ----------
Sepulchre, J.-A., Merajver, S.D., Ventura, A.C.
"Retroactive signaling in short signaling pathways"
. PLoS ONE, vol. 7, no. 7, 2012.
http://dx.doi.org/10.1371/journal.pone.0040806---------- VANCOUVER ----------
Sepulchre, J.-A., Merajver, S.D., Ventura, A.C. Retroactive signaling in short signaling pathways. PLoS ONE. 2012;7(7).
http://dx.doi.org/10.1371/journal.pone.0040806