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通过对蛋白激酶突变体的系统筛选揭示细胞分化的调控复杂性。

Regulatory complexity of cellular differentiation in revealed through systematic screening of protein kinase mutants.

机构信息

Department of Microbiology and Molecular Genetics, University of Texas McGovern Medical School, Houston, Texas, USA.

出版信息

mBio. 2024 Aug 14;15(8):e0169824. doi: 10.1128/mbio.01698-24. Epub 2024 Jul 26.

DOI:10.1128/mbio.01698-24
PMID:39058031
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11323536/
Abstract

A recent study in reports the construction and preliminary screening of a library containing mutants of 99 of the 119 predicted protein kinases in (the majority of the remaining 20 are probably essential) (J. Kramara, M.-J. Kim, T. L. Ollinger, L. C. Ristow, et al., mBio e01249-24, 2024, https://doi.org/10.1128/mbio.01249-24). Using a quantitative competition assay in 10 conditions that represent nutritional, osmotic, cell wall, and pH stresses that are considered to model various aspects of the host environment allowed them to phenotypically cluster kinases, which highlight both the integration and specialization of signaling pathways, suggesting novel functions for many kinases. In addition, they tackle two complex and partially overlapping differentiation events, hyphal morphogenesis and biofilm formation. They find that a remarkable 88% of the viable kinase mutants in affect hyphal growth, illustrating how integrated morphogenesis is in the overall biology of this organism, and begin to dissect the regulatory relationships that control this key virulence trait.

摘要

最近一项在 中报告的研究,构建并初步筛选了一个文库,其中包含了 中的 119 个预测蛋白激酶中的 99 个突变体(其余的 20 个激酶可能大多是必需的)(J. Kramara、M.-J. Kim、T. L. Ollinger、L. C. Ristow 等人,mBio e01249-24,2024,https://doi.org/10.1128/mbio.01249-24)。他们使用了 10 种定量竞争测定条件,这些条件代表了营养、渗透压、细胞壁和 pH 压力,这些条件被认为可以模拟宿主环境的各个方面,从而使激酶能够表型聚类,这突出了信号通路的整合和专业化,暗示了许多激酶的新功能。此外,它们还解决了两个复杂且部分重叠的分化事件,菌丝形态发生和生物膜形成。他们发现, 在 中 88%的有活力的激酶突变体影响菌丝生长,这说明了形态发生的整合在该生物体的整体生物学中是多么重要,并开始剖析控制这一关键毒力特性的调控关系。

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本文引用的文献

1
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mBio. 2024 Aug 14;15(8):e0124924. doi: 10.1128/mbio.01249-24. Epub 2024 Jul 1.
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Application of the Mutant Libraries for Functional Genomics.突变文库在功能基因组学中的应用。
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Candida albicans Filamentation Does Not Require the cAMP-PKA Pathway .白色念珠菌菌丝体的形成不需要 cAMP-PKA 途径。
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