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由细胞类型特异性和非特异性元件组成的丝裂原活化蛋白激酶级联反应控制着真菌病原体新型隐球菌的交配和分化。

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

作者信息

Davidson Robert C, Nichols Connie B, Cox Gary M, Perfect John R, Heitman Joseph

机构信息

Department of Molecular Genetics, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

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

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.

摘要

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。

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