Hysteretic and graded responses in bacterial two-component signal transduction

Oleg A. Igoshin, Rui Alves, Michael A. Savageau

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Bacterial two-component systems (TCS) are key signal transduction networks regulating global responses to environmental change. Environmental signals may modulate the phosphorylation state of sensor kinases (SK). The phosphorylated SK transfers the phosphate to its cognate response regulator (RR), which causes physiological response to the signal. Frequently, the SK is bifunctional and, when unphosphorylated, it is also capable of dephosphorylating the RR. The phosphatase activity may also be modulated by environmental signals. Using the EnvZ/OmpR system as an example, we constructed mathematical models to examine the steady-state and kinetic properties of the network. Mathematical modelling reveals that the TCS can show bistable behaviour for a given range of parameter values if unphosphorylated SK and RR form a dead-end complex that prevents SK autophosphorylation. Additionally, for bistability to exist the major dephosphorylation flux of the RR must not depend on the unphosphorylated SK. Structural modelling and published affinity studies suggest that the unphosphorylated SK EnvZ and the RR OmpR form a dead-end complex. However, bistability is not possible because the dephosphorylation of OmpR∼P is mainly done by unphosphorylated EnvZ. The implications of this potential bistability in the design of the EnvZ/OmpR network and other TCS are discussed.

Original languageEnglish (US)
Pages (from-to)1196-1215
Number of pages20
JournalMolecular Microbiology
Volume68
Issue number5
DOIs
StatePublished - Jun 2008

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Signal Transduction
Phosphotransferases
Phosphoric Monoester Hydrolases
Theoretical Models
Phosphates
Phosphorylation

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Hysteretic and graded responses in bacterial two-component signal transduction. / Igoshin, Oleg A.; Alves, Rui; Savageau, Michael A.

In: Molecular Microbiology, Vol. 68, No. 5, 06.2008, p. 1196-1215.

Research output: Contribution to journalArticle

Igoshin, Oleg A. ; Alves, Rui ; Savageau, Michael A. / Hysteretic and graded responses in bacterial two-component signal transduction. In: Molecular Microbiology. 2008 ; Vol. 68, No. 5. pp. 1196-1215.
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