Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5

Mol Cell. 2008 Jun 6;30(5):649-56. doi: 10.1016/j.molcel.2008.04.016.

Abstract

Cell differentiation requires the ability to detect and respond appropriately to a variety of extracellular signals. Here we investigate a differentiation switch induced by changes in the concentration of a single stimulus. Yeast cells exposed to high doses of mating pheromone undergo cell division arrest. Cells at intermediate doses become elongated and divide in the direction of a pheromone gradient (chemotropic growth). Either of the pheromone-responsive MAP kinases, Fus3 and Kss1, promotes cell elongation, but only Fus3 promotes chemotropic growth. Whereas Kss1 is activated rapidly and with a graded dose-response profile, Fus3 is activated slowly and exhibits a steeper dose-response relationship (ultrasensitivity). Fus3 activity requires the scaffold protein Ste5; when binding to Ste5 is abrogated, Fus3 behaves like Kss1, and the cells no longer respond to a gradient or mate efficiently with distant partners. We propose that scaffold proteins serve to modulate the temporal and dose-response behavior of the MAP kinase.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cell Differentiation / drug effects
  • Enzyme Activation
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Pheromones / pharmacology
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Pheromones
  • STE5 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • FUS3 protein, S cerevisiae
  • KSS1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinases