title: A MAP kinase cascade composed of cell type specific and non-specific elements controls mating and differentiation of the fungal pathogen Cryptococcus neoformans.
abstract: 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.
authors.affiliation: Department of Molecular Genetics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Davidson
authors.forename: Connie B
authors.initials: CB
authors.lastname: Nichols
authors.forename: Gary M
authors.initials: GM
authors.lastname: Cox
authors.forename: John R
authors.initials: JR
authors.lastname: Perfect
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D003455:Cryptococcus neoformans / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D049770:Genes, Mating Type, Fungal; D006238:Haploidy; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D051379:Mice; D008811:Mice, Inbred DBA; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D014774:Virulence
chemical_list: D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020930:MAP Kinase Kinase Kinases; C067018:Ste11 protein, S cerevisiae; D020929:Mitogen-Activated Protein Kinase Kinases; C119844:STE7 protein, S cerevisiae