Skip to main content

Bistability in One Equation or Fewer

  • Protocol
  • First Online:
Computational Modeling of Signaling Networks

Part of the book series: Methods in Molecular Biology ((MIMB,volume 880))

Abstract

When several genes or proteins modulate one another’s activity as part of a network, they sometimes produce behaviors that no protein could accomplish on its own. Intuition for these emergent behaviors often cannot be obtained simply by tracing causality through the network in discreet steps. Specifically, when a network contains a feedback loop, biologists need specialized tools to understand the network’s behaviors and their necessary conditions. This analysis is grounded in the mathematics of ordinary differential equations. We, however, will demonstrate the use of purely graphical methods to determine, for experimental data, the plausibility of two network behaviors, bistability and irreversibility. We use the Xenopus laevis oocyte maturation network as our example, and we make special use of iterative stability analysis, a graphical tool for determining stability in two dimensions.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Huang CY, Ferrell JE Jr (1996 ) Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA 93(19):10078–10083

    Article  PubMed  CAS  Google Scholar 

  2. Matten WT, Copeland TD, Ahn NG, Vande Woude GF (1996) Positive feedback between MAP kinase and Mos during Xenopus oocyte maturation. Dev Biol 179:485–492

    Article  PubMed  CAS  Google Scholar 

  3. Bagowski CP, Besser J, Frey CR, Ferrell JE Jr (2003) The JNK cascade as a biochemical switch in mammalian cells: ultrasensitive and all-or-none responses. Curr Biol 13(4):315–320

    Article  PubMed  CAS  Google Scholar 

  4. Bagowski CP, Ferrell JE Jr. Bistability in the JNK cascade. Curr. Biol. 2001 11, 1176–1182.

    Article  PubMed  CAS  Google Scholar 

  5. Kim SY, Ferrell JE Jr (2007) Substrate competition as a source of ultrasensitivity in the inactivation of Wee1. Cell 128(6):1133–1145

    Article  PubMed  CAS  Google Scholar 

  6. Ferrell JE Jr (1996) Tripping the switch fantastic: how a protein kinase cascade can convert graded inputs into switch-like outputs. Trends Biochem Sci 21(12):460–466

    Article  PubMed  CAS  Google Scholar 

  7. Burack WR, Sturgill TW (1997) The activating dual phosphorylation of MAPK by MEK is nonprocessive. Biochemistry 36:5929–5933

    Article  PubMed  CAS  Google Scholar 

  8. Chen M, Li D, Krebs EG, Cooper JA (1997) The casein kinase II beta subunit binds to Mos and inhibits Mos activity. Mol Cell Biol 17:1904–1912

    PubMed  CAS  Google Scholar 

  9. Ferrell JE Jr (1997) How responses get more switch-like as you move down a protein kinase cascade. Trends Biochem Sci 22:288–289

    Article  PubMed  CAS  Google Scholar 

  10. Ferrell JE Jr (1999) Building a cellular switch: more lessons from a good egg. Bioessays 21(10):866–870

    Article  PubMed  Google Scholar 

  11. Ferrell JE Jr (2008) Feedback regulation of opposing enzymes generates robust, all-or-none bistable responses. Curr Biol 18(6):R244–R245

    Article  PubMed  CAS  Google Scholar 

  12. Markevich NI, Hoek JB, Kholodenko BN (2004) Signalling switches and bistability arising from multisite phosphorylation in protein kinase cascades. J Cell Biol 164:353–359

    Article  PubMed  CAS  Google Scholar 

  13. Goldbeter A, Koshland DE (1981) An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci USA 78(11): 6840–6844.

    Article  PubMed  CAS  Google Scholar 

  14. Goldbeter A, Koshland DE Jr (1982) Sensitivity amplification in biochemical systems. Q Rev Biophys 15:555–591

    Article  PubMed  CAS  Google Scholar 

  15. Ferrell JE Jr (2002) Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14:140–148

    Article  PubMed  CAS  Google Scholar 

  16. Lisman JE (1985) A mechanism for memory storage insensitive to molecular turnover: a bistable autophosphorylating kinase. Proc Natl Acad Sci USA 82:3055–3057

    Article  PubMed  CAS  Google Scholar 

  17. Thomas R, Kaufman M (2001) Multistationarity, the basis of cell differentiation and memory. I. Structural conditions of multistationarity and other nontrivial behavior. Chaos 11:170–179

    Google Scholar 

  18. Ferrell JE Jr, Machleder EM (1998) The biochemical basis of an all-or-none cell fate switch in Xenopus oocytes. Science 280(5365):895–898

    Article  PubMed  CAS  Google Scholar 

  19. Xiong W, Ferrell JE Jr (2003) A positive-feedback-based ‘memory module’ that governs a cell fate decision. Nature 426(6965):460–465

    Article  PubMed  CAS  Google Scholar 

  20. To TL, Maheshri N (2010) Noise can induce bimodality in positive transcriptional feedback loops without bistability. Science 327(5969):1142–1145

    Article  PubMed  CAS  Google Scholar 

  21. Pomerening JR, Sontag ED, Ferrell JE Jr (2003) Building a cell cycle oscillator: hysteresis and bistability in the activation of Cdc2. Nat Cell Biol 5:346–351

    Article  PubMed  CAS  Google Scholar 

  22. Ferrell JE Jr, Xiong W (2010) Bistability in cell signalling: how to make continuous processes discontinuous, and reversible processes rreversible. Chaos 11:227–236

    Article  Google Scholar 

  23. S. Strogatz, (2001) “Nonlinear dynamics and chaos,” Westview Press; 1 edition

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xuedong Liu .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Anderson, G.A., Liu, X., Ferrell, J.E. (2012). Bistability in One Equation or Fewer. In: Liu, X., Betterton, M. (eds) Computational Modeling of Signaling Networks. Methods in Molecular Biology, vol 880. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-833-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-61779-833-7_4

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61779-832-0

  • Online ISBN: 978-1-61779-833-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics