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Temporal Quantification of MAPK Induced Expression in Single Yeast Cells
07:59

Temporal Quantification of MAPK Induced Expression in Single Yeast Cells

Published on: October 4, 2013

8.9K

Mathematical modeling reveals differential regulation of MAPK activity by phosphatase proteins in the yeast pheromone

Nathan Dyjack1, Cassandra Azeredo-Tseng, Necmettin Yildirim

  • 1Division of Natural Sciences, New College of Florida, 5800 Bayshore Road, Sarasota, FL 34243, USA. nyildirim@ncf.edu.

Molecular Biosystems
|June 6, 2017
PubMed

Insights

Cells adapt to signals using feedback mechanisms. Two yeast phosphatases, Ptp3 and Msg5, regulate the mitogen-activated protein kinase (MAPK) pathway, with Ptp3 acting early and Msg5 later, ensuring controlled cellular responses.

Area of Science:

  • Cellular biology
  • Systems biology
  • Biochemistry

Background:

  • Cells employ adaptation mechanisms to prevent indefinite responses to external signals.
  • The yeast mating-response pathway serves as a model for studying adaptation to persistent signals.
  • This pathway involves a mitogen-activated protein kinase (MAPK) cascade with two negative feedback inhibitions mediated by phosphatases Ptp3 and Msg5.

Purpose of the Study:

  • To investigate the biological significance of two distinct negative feedback mechanisms acting on the phosphorylated MAPK protein Fus3 (pFus3).
  • To mathematically model and quantify the inhibitory roles of Ptp3 and Msg5 on pFus3 dynamics using published experimental data.

Main Methods:

  • Development of a mathematical model based on existing experimental data.
  • Quantitative analysis of the inhibitory effects of Ptp3 and Msg5 on pFus3.
  • Analysis of signal profile dependency and temporal impact of feedback inhibitions.

Main Results:

  • Ptp3-mediated inhibition of pFus3 is largely signal-independent and most effective at early time points.
  • Msg5-mediated inhibition of pFus3 is highly signal-dependent and influential after pFus3 reaches maximum abundance.
  • Ptp3 reduces early pFus3 dynamics variation, while Msg5's noise-reduction effects increase over time.

Conclusions:

  • Distinct temporal roles of Ptp3 and Msg5 contribute to the precise regulation of the yeast mating-response pathway.
  • The dual feedback system ensures robust adaptation to external signals by modulating pFus3 activity at different stages.
  • Mathematical modeling provides insights into the quantitative contributions of individual feedback components to cellular adaptation.

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