Davidson Robert C, Nichols Connie B, Cox Gary M, Perfect John R, Heitman Joseph
Department of Molecular Genetics, Duke University Medical Center, Durham, NC 27710, USA.
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.
新型隐球菌是一种机会性真菌病原体，具有明确的有性生殖周期，其中交配型位点的α等位基因与毒力和单倍体分化相关联。在这里，我们分析了一个由交配型特异性（Ste11α、Ste12α）和非特异性（Ste7、Cpk1）元件组成的保守丝裂原活化蛋白激酶（MAPK）级联反应。基因敲除实验表明，这种特殊的MAPK途径对于交配和细胞类型特异性分化都是必需的，但对毒力并非必需。发现Ste11α、Ste7和Cpk1激酶作为一个协同信号模块起作用，而Ste12α转录因子则与一个冗余伙伴一起发挥作用，或者在一个分支或平行信号通路中发挥作用。我们的研究说明了MAPK级联反应是如何由细胞类型特异性和非特异性成分构建而成的，从而产生有助于细胞类型特异性信号传导和分化模式的途径。
