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PLOS ONE  2012 

Noise Propagation in Two-Step Series MAPK Cascade

DOI: 10.1371/journal.pone.0035958

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Abstract:

Series MAPK enzymatic cascades, ubiquitously found in signaling networks, act as signal amplifiers and play a key role in processing information during signal transduction in cells. In activated cascades, cell-to-cell variability or noise is bound to occur and thereby strongly affects the cellular response. Commonly used linearization method (LM) applied to Langevin type stochastic model of the MAPK cascade fails to accurately predict intrinsic noise propagation in the cascade. We prove this by using extensive stochastic simulations for various ranges of biochemical parameters. This failure is due to the fact that the LM ignores the nonlinear effects on the noise. However, LM provides a good estimate of the extrinsic noise propagation. We show that the correct estimate of intrinsic noise propagation in signaling networks that contain at least one enzymatic step can be obtained only through stochastic simulations. Noise propagation in the cascade depends on the underlying biochemical parameters which are often unavailable. Based on a combination of global sensitivity analysis (GSA) and stochastic simulations, we developed a systematic methodology to characterize noise propagation in the cascade. GSA predicts that noise propagation in MAPK cascade is sensitive to the total number of upstream enzyme molecules and the total number of molecules of the two substrates involved in the cascade. We argue that the general systematic approach proposed and demonstrated on MAPK cascade must accompany noise propagation studies in biological networks.

References

[1]  Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen Activated Protein Kinase: Conservation of a three-kinase module from yeast to human. Physiol. Rev. 79: 143–180.
[2]  Zhang YL, Dong C (2005) MAP kinases in immune responses. Cellular and Molecular Immunology 2: 20–27.
[3]  Huang CY, Ferrell JE Jr (1996) Ultrasensitivity in the mitogen activated protein kinase cascades. Proc Natl Acad Sci U S A 93: 10078–10083.
[4]  Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410: 37–40.
[5]  Zhang YL, Dong C (2007) Regulatory mechanisms of mitogen-activated kinase signaling. Cellular and Molecular Life Sciences. 64: 2771–2789.
[6]  Dhanasekaran DN, Johnson GL (2007) MAPKs: function, regulation, role in cancer and therapeutic targeting. Oncogene 26: 3097–3099.
[7]  Qi M, Elion EA (2005) MAP kinase pathways. J. Cell. Sci. 118: 3569–3572.
[8]  Lee JC, Kassis S, Kumar S, Badger A, Adams JL (1999) p38 Mitogen Activated Protein Kinase inhibitors – Mechanisms and therapeutic potentials. Pharmacology and Therapeutics 82: 389–397.
[9]  T?nase-Nicola S, Warren PB, ten Wolde PR (2006) Signal detection, modularity, and the correlation between extrinsic and intrinsic noise in biochemical networks. Phys Rev Lett 97: 068102.
[10]  Spencer SL, Gaudet S, Albeck JG, Burke JM, Sorger PK (2009) Non-genetic origins of cell-to-cell variability in TRAIL-induced apoptosis. Nature 459: 428–432.
[11]  Rao CV, Wolf DM, Arkin AP (2002) Control, exploitation and tolerance of intracellular noise. Nature 420: 21–237.
[12]  Raser JM, O'Shea EK (2005) Noise in gene expression: Origins, consequences, and control. Science 309: 2010–2013.
[13]  Raj A, van Oudenaarden A (2008) Nature, nurture, or chance: Stochastic gene expression and its consequences. Cell 135: 216–226.
[14]  McDonnell MD, Ward LM (2011) The benefits of noise in neural systems: Bridging theory and experiment. Nat Rev Neurosci 12: 415–425.
[15]  Paszek P, Ryan S, Ashall L, Sillitoe K, Harper CV, et al. (2010) Population robustness arising from cellular heterogeneity. Proc Natl Acad Sci U S A 107: 11644–11649.
[16]  Eldar A, Elowitz MB (2010) Functional roles for noise in genetic circuits. Nature 467: 167–173.
[17]  Feinerman O, Veiga J, Dorfman JR, Germain RN, Altan-Bonnet G (2008) Variability and robustness in T-cell activation from regulated heterogeneity in protein levels. Science 321: 1081–1084.
[18]  Suel GM, Kulkarni RP, Dworkin J, Garcia-Ojalvo J, Elowitz MB (2007) Tunability and noise dependence in differentiation dynamics. Science 315: 1716–1719.
[19]  Weinberger LS, Burnett JC, Toettcher JE, Arkin AP, Schaffer DV (2005) Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 tat fluctuations drive phenotypic diversity. Cell 122: 169–182.
[20]  You L, Cox RS III, Weiss R, Arnold FH (2004) Programmed population control by cell-cell communication and regulated killing. Nature 428: 868–871.
[21]  McAdams HH, Arkin A (1999) It's a noisy business! Genetic regulation at the nanomolar scale. Trends in Genetics 15: 65–69.
[22]  Barkai N, Leibler S (2000) Biological rhythms: Circadian clocks limited by noise. Nature 403: 267–268.
[23]  Allen C, Stevens CF (1994) An evaluation of causes for unreliability of synaptic transmission. Proc Natl Acad Sci U S A 91: 10380–10383.
[24]  White JA, Rubinstein JT, Kay AR (2000) Channel noise in neurons. Trends in Neurosc 23: 131–137.
[25]  van Oudenaarden A, Theriot JA (1999) Cooperative symmetry-breaking by actin polymerization in a model for cell motility. Nat Cell Biol 1: 493–499.
[26]  Thattai M, van Oudenaarden A (2002) Attenuation of noise in ultrasensitive signaling cascades. Biophysical J 82: 2943–2950.
[27]  Shibata T, Fujimoto K (2005) Noisy signal amplification in ultrasensitive signal transduction. Proc Natl Acad Sci U S A 102: 331–336.
[28]  Kholodenko BN (2006) Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 7: 165–176.
[29]  Detwiler PB, Ramanathan S, Sengupta A, Shraiman BI (2000) Engineering aspects of enzymatic signal transduction: Photoreceptors in the retina. Biophysical J. 79: 2801–2817.
[30]  Viswanathan G, Jayaprakash C, Sealfon SC, Hayot , F (2008) Shared kinase fluctuations between two enzymatic reactions. Phys Biol 5: 046002.
[31]  Elf J, Ehrenberg M (2003) Fast evaluation of fluctuations in biochemical networks with the linear noise approximation. Genome Res 13: 2475–2484.
[32]  Jachimowski CJ, McQuarrie DA, Russell ME (1964) A stochastic approach to enzyme-substrate reactions. Biochemistry 3: 1732–1736.
[33]  Rao CV, Arkin AP (2003) Stochastic chemical kinetics and the quasi-steady-state assumption: Application to the Gillespie algorithm. J of Chem Phys. 118: 4999–5010.
[34]  van Kampen, NG (1992) Stochastic Processes in Physics and Chemistry. 463 p. 3rd Edition. Elsevier.
[35]  Fujioka A, Terai K, Itoh RE, Aoki K, Nakamura T, et al. (2006) Dynamics of the Ras/ERK MAPK cascade as monitored by fluorescent probes. J Biol Chem 281: 8917–8926.
[36]  Seydel R, Hlavacek V (1987) Role of continuation in engineering analysis. Chem Engg Sci 42: 1281–1295.
[37]  Goldbeter A, Koshland DE Jr (1981) An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci 78: 6840–6844.
[38]  Ciliberto A, Capuani F, Tyson JJ (2007) Modeling networks of coupled enzymatic reactions using the total quasi-steady state approximation. PLoS Comput Biol 3: e45.
[39]  Craciun G, Tang Y, Feinberg M (2006) Understanding bistability in complex enzyme-driven reaction networks. Proc Natl Acad Sci U S A 103: 8697–8702.
[40]  Jiménez-Aquino JI (1996) The characteristic times of the transient stochastic dynamics with time-dependent control parameters: Distributed initial conditions. Physica A 229: 444–460.
[41]  Jiménez-Aquino JI (1997) Multivariate formulation of transient stochastic dynamics. Physica A 237: 113–122.
[42]  Santos SDM, Verveer PJ, Bastiaens PIH (2007) Growth factor-induced MAPK network topology shapes Erk response determining PC-12 cell fate. Nat Cell Biol 9: 324–330.
[43]  Ruf F, Hayot F, Park M-J, Ge Y, et al. (2007) Noise propagation and scaling in regulation of Gonadotrope biosynthesis. Biophy J 93: 4474–4480.
[44]  Higham DJ (2001) An algorithmic introduction to numerical simulation of stochastic differential equations. SIAM Review 43: 525–546.
[45]  Samoilov M, Plyasunov S, Arkin AP (2005) Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations. Proc Natl Acad Sci U S A 102: 2310–2315.
[46]  Grima R, Thomas P, Straube AV (2011) How accurate are the nonlinear chemical Fokker-Planck and chemical Langevin equations? J Chem Phys 135: 084103.
[47]  Lan Y, Papoian GA (2006) The interplay between discrete noise and nonlinear chemical kinetics in a signal amplification cascade. J Chem Phys 125: 154901–12.
[48]  Gillespie DT (1976) A general method for numerically simulating the stochastic time evolution of coupled chemical reactions. J Comp Phys 22: 403–434.
[49]  Alon U (2007) An Introduction to Systems Biology: Design Principles of Biological Circuits. Mathematical and Computational Biology Series, Vol. 10, Chapman and Hall/CRC, Taylor & Francis Group. 301 p.
[50]  Jianfang J, Hong Y, Taiyuan L, Hong W (2007) Global sensitivity analysis of cell signalling transduction networks based on Latin Hypercube Sampling method. The 1st Internat Conf on Bioinf Biomed Engng 1: 442–445.
[51]  Segel LA (1988) On the validity of the steady state assumption of enzyme kinetics. Bull Math Biol 50: 579–593.
[52]  Park SH, Zarrinpar A, Lim WA (2003) Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299: 1061–1064.
[53]  Angeli D, Ferrell JE Jr, Sontag ED (2004) Detection of multistability, bifurcations, and hysteresis in a large class of biological positive-feedback systems. Proc Natl Acad Sci U S A 101: 1822–1827.
[54]  Favata MF, Horiuchi KY, Manos EJ, Daulerio AJ, Stradley DA, et al. (1988) Identification of a novel inhibitor of Mitogen-activated Protein Kinase Kinase. J Biol Chem 273: 18623–18632.
[55]  English JM, Cobb MH (2002) Pharmacological inhibitors of MAPK pathways. Trends Pharmacol Sci 23: 40–45.
[56]  Bashor CJ, Helman NC, Yan S, Lim WA (2008) Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics. Science 319: 1539–1543.
[57]  Gillespie DT (1992) A rigorous derivation of the chemical master equation. Physica A: Stat Mech and its Appl 188: 404–425.
[58]  Gardiner CW (1990) Handbook of stochastic methods for physics, chemistry and the natural sciences. Springer. 442 p.
[59]  Iman RL, Conovera WJ (1980) Small sample sensitivity analysis techniques for computer models.with an application to risk assessment. Comm in Stat – Theory and Meth 9: 1749–1842.

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