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A Novel Phosphoregulatory Switch Controls the Activity and Function of the Major Catalytic Subunit of Protein Kinase A in Aspergillus fumigatus.一种新型磷酸化调节开关控制烟曲霉中蛋白激酶A主要催化亚基的活性和功能。
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3
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Divergent Protein Kinase A isoforms co-ordinately regulate conidial germination, carbohydrate metabolism and virulence in Aspergillus fumigatus.不同的蛋白激酶 A 同工型协同调控烟曲霉分生孢子的萌发、碳水化合物代谢和毒力。
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烟曲霉PkaR的磷酸化通过新机制影响生长和细胞壁完整性。

Phosphorylation of Aspergillus fumigatus PkaR impacts growth and cell wall integrity through novel mechanisms.

作者信息

Shwab Elliot K, Juvvadi Praveen R, Waitt Greg, Soderblom Erik J, Moseley Martin A, Nicely Nathan I, Steinbach William J

机构信息

Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, NC, USA.

Duke Proteomics and Metabolomics Core Facility, Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.

出版信息

FEBS Lett. 2017 Nov;591(22):3730-3744. doi: 10.1002/1873-3468.12886. Epub 2017 Nov 9.

DOI:10.1002/1873-3468.12886
PMID:29067690
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5705279/
Abstract

Protein kinase A (PKA) signaling is essential for growth and virulence of the fungal pathogen Aspergillus fumigatus. Little is known concerning the regulation of this pathway in filamentous fungi. Employing liquid chromatography-tandem mass spectroscopy, we identified novel phosphorylation sites on the regulatory subunit PkaR, distinct from those previously identified in mammals and yeasts, and demonstrated the importance of two phosphorylation clusters for hyphal growth and cell wall-stress response. We also identified key differences in the regulation of PKA subcellular localization in A. fumigatus compared with other species. This is the first analysis of the phosphoregulation of a PKA regulatory subunit in a filamentous fungus and uncovers critical mechanistic differences between PKA regulation in filamentous fungi compared with mammals and yeast species, suggesting divergent targeting opportunities.

摘要

蛋白激酶A（PKA）信号传导对于真菌病原体烟曲霉的生长和毒力至关重要。关于丝状真菌中该信号通路的调控，我们了解甚少。通过液相色谱-串联质谱分析，我们在调节亚基PkaR上鉴定出了新的磷酸化位点，这些位点不同于先前在哺乳动物和酵母中鉴定出的位点，并证明了两个磷酸化簇对菌丝生长和细胞壁应激反应的重要性。我们还发现，与其他物种相比，烟曲霉中PKA亚细胞定位的调控存在关键差异。这是对丝状真菌中PKA调节亚基磷酸化调控的首次分析，揭示了丝状真菌与哺乳动物和酵母物种在PKA调控方面的关键机制差异，提示了不同的靶向机会。