Rho1 GTPase and PKC ortholog Pck1 are upstream activators of the cell integrity MAPK pathway in fission yeast

PLoS One. 2014 Jan 31;9(1):e88020. doi: 10.1371/journal.pone.0088020. eCollection 2014.

Abstract

In the fission yeast Schizosaccharomyces pombe the cell integrity pathway (CIP) orchestrates multiple biological processes like cell wall maintenance and ionic homeostasis by fine tuning activation of MAPK Pmk1 in response to various environmental conditions. The small GTPase Rho2 positively regulates the CIP through protein kinase C ortholog Pck2. However, Pmk1 retains some function in mutants lacking either Rho2 or Pck2, suggesting the existence of additional upstream regulatory elements to modulate its activity depending on the nature of the environmental stimulus. The essential GTPase Rho1 is a candidate to control the activity of the CIP by acting upstream of Pck2, whereas Pck1, a second PKC ortholog, appears to negatively regulate Pmk1 activity. However, the exact regulatory nature of these two proteins within the CIP has remained elusive. By exhaustive characterization of strains expressing a hypomorphic Rho1 allele (rho1-596) in different genetic backgrounds we show that both Rho1 and Pck1 are positive upstream regulatory members of the CIP in addition to Rho2 and Pck2. In this new model Rho1 and Rho2 control Pmk1 basal activity during vegetative growth mainly through Pck2. Notably, whereas Rho2-Pck2 elicit Pmk1 activation in response to most environmental stimuli, Rho1 drives Pmk1 activation through either Pck2 or Pck1 exclusively in response to cell wall damage. Our study reveals the intricate and complex functional architecture of the upstream elements participating in this signaling pathway as compared to similar routes from other simple eukaryotic organisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinases / genetics
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Schizosaccharomyces / enzymology*
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Rho2 protein, S pombe
  • Schizosaccharomyces pombe Proteins
  • Pck1 protein, S pombe
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases
  • Pmk1 protein, S pombe
  • rho GTP-Binding Proteins
  • rho1 protein, S pombe

Grants and funding

This work was supported by grants BFU2011-22517 (Ministerio de Economía y Competitividad) and 15280/PI/10 (Fundación Séneca, Región de Murcia), Spain to J.C., and BFU2010-15641 (Ministerio de Economía y Competitividad) to P.P. ERDF (European Regional Development Fund) co-funding was received from the EU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.