The Saccharomyces cerevisiae Ptc1 protein phosphatase attenuates G2-M cell cycle blockage caused by activation of the cell wall integrity pathway

Mol Microbiol. 2016 Aug;101(4):671-87. doi: 10.1111/mmi.13416. Epub 2016 Jun 3.

Abstract

Lack of the yeast Ptc1 Ser/Thr protein phosphatase results in numerous phenotypic defects. A parallel search for high-copy number suppressors of three of these phenotypes (sensitivity to Calcofluor White, rapamycin and alkaline pH), allowed the isolation of 25 suppressor genes, which could be assigned to three main functional categories: maintenance of cell wall integrity (CWI), vacuolar function and protein sorting, and cell cycle regulation. The characterization of these genetic interactions strengthens the relevant role of Ptc1 in downregulating the Slt2-mediated CWI pathway. We show that under stress conditions activating the CWI pathway the ptc1 mutant displays hyperphosphorylated Cdc28 kinase and that these cells accumulate with duplicated DNA content, indicative of a G2-M arrest. Clb2-associated Cdc28 activity was also reduced in ptc1 cells. These alterations are attenuated by mutation of the MKK1 gene, encoding a MAP kinase kinase upstream Slt2. Therefore, our data show that Ptc1 is required for proper G2-M cell cycle transition after activation of the CWI pathway.

MeSH terms

  • CDC28 Protein Kinase, S cerevisiae / genetics
  • CDC28 Protein Kinase, S cerevisiae / metabolism
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Division / physiology
  • Cell Wall / genetics
  • Cell Wall / metabolism
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Protein Phosphatase 2 / genetics
  • Protein Phosphatase 2 / metabolism*
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Saccharomyces cerevisiae Proteins
  • CDC28 Protein Kinase, S cerevisiae
  • MKK1 protein, S cerevisiae
  • Mitogen-Activated Protein Kinase Kinases
  • PTC1 protein, S cerevisiae
  • Protein Phosphatase 2