Candida glabrata Ste20 is involved in maintaining cell wall integrity and adaptation to hypertonic stress, and is required for wild-type levels of virulence

Yeast. 2004 May;21(7):557-68. doi: 10.1002/yea.1125.

Abstract

The conserved family of fungal Ste20 p21-activated serine-threonine protein kinases regulate several signalling cascades. In Saccharomyces cerevisiae Ste20 is involved in pheromone signalling, invasive growth, the hypertonic stress response, cell wall integrity and binds Cdc42, a Rho-like small GTP-binding protein required for polarized morphogenesis. We have cloned the STE20 homologue from the fungal pathogen Candida glabrata and have shown that it is present in a single copy in the genome. Translation of the nucleotide sequence predicts that C. glabrata Ste20 contains a highly conserved p21-activated serine-threonine protein kinase domain, a binding site for G-protein beta subunits and a regulatory Rho-binding domain that enables the kinase to interact with Cdc42 and/or Rho-like small GTPases. C. glabrata Ste20 has 53% identity and 58% predicted amino acid similarity to S. cerevisiae Ste20 and can complement both the nitrogen starvation-induced filamentation and mating defects of S. cerevisiae ste20 mutants. Analysis of ste20 null and disrupted strains suggest that in C. glabrata Ste20 is required for a fully functional hypertonic stress response and intact cell wall integrity pathway. C. glabrata Ste20 is not required for nitrogen starvation-induced filamentation. Survival analysis revealed that C. glabrata ste20 mutants, while still able to cause disease, are mildly attenuated for virulence compared to reconstituted STE20 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Candida glabrata / enzymology
  • Candida glabrata / genetics
  • Candida glabrata / pathogenicity
  • Candida glabrata / physiology*
  • Candidiasis / microbiology*
  • Cell Wall / enzymology
  • Cell Wall / physiology
  • Cloning, Molecular
  • DNA, Fungal / chemistry
  • DNA, Fungal / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • Genetic Complementation Test
  • Intracellular Signaling Peptides and Proteins
  • MAP Kinase Kinase Kinases
  • Mice
  • Molecular Sequence Data
  • Mutagenesis, Insertional
  • Polymerase Chain Reaction
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins*
  • Sequence Alignment
  • Virulence

Substances

  • DNA, Fungal
  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein-Serine-Threonine Kinases
  • MAP Kinase Kinase Kinases
  • STE20 protein, S cerevisiae