A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans

Mol Microbiol. 2003 Jul;49(2):469-85. doi: 10.1046/j.1365-2958.2003.03563.x.


Cryptococcus neoformans is an opportunistic fungal pathogen with a defined sexual cycle in which the alpha allele of the mating type locus is linked to virulence and haploid differentiation. Here we analysed a conserved MAP kinase cascade composed of mating-type specific (Ste11alpha, Ste12alpha) and non-specific (Ste7, Cpk1) elements. Gene disruption experiments demonstrate that this specialized MAP kinase pathway is required for both mating and cell type-specific differentiation but not for virulence. The Ste11alpha, Ste7 and Cpk1 kinases were found to act as a co-ordinate signalling module, whereas the Ste12alpha transcription factor functions with a redundant partner or in a branched or parallel signalling pathway. Our studies illustrate how MAP kinase cascades can be constructed from cell type-specific and non-specific components, yielding pathways that contribute to cell type-specific patterns of signalling and differentiation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cryptococcus neoformans / genetics
  • Cryptococcus neoformans / pathogenicity
  • Cryptococcus neoformans / physiology*
  • Female
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genes, Fungal
  • Genes, Mating Type, Fungal
  • Haploidy
  • Humans
  • MAP Kinase Kinase Kinases / metabolism
  • MAP Kinase Signaling System / physiology*
  • Mice
  • Mice, Inbred DBA
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinases / metabolism*
  • Protein Kinases / metabolism
  • Saccharomyces cerevisiae Proteins / metabolism
  • Virulence


  • Fungal Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • Ste11 protein, S cerevisiae
  • Mitogen-Activated Protein Kinase Kinases
  • STE7 protein, S cerevisiae