González-Rubio Gema, Sastre-Vergara Lucía, Molina María, Martín Humberto, Fernández-Acero Teresa
Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad Complutense de Madrid, and Instituto Ramón y Cajal de Investigaciones Sanitarias (IRYCIS), 28040 Madrid, Spain.
J Fungi (Basel). 2022 Apr 4;8(4):368. doi: 10.3390/jof8040368.
The cell wall integrity (CWI) MAPK pathway of budding yeast is specialized in responding to cell wall damage, but ongoing research shows that it participates in many other stressful conditions, suggesting that it has functional diversity. The output of this pathway is mainly driven by the activity of the MAPK Slt2, which regulates important processes for yeast physiology such as fine-tuning of signaling through the CWI and other pathways, transcriptional activation in response to cell wall damage, cell cycle, or determination of the fate of some organelles. To this end, Slt2 precisely phosphorylates protein substrates, modulating their activity, stability, protein interaction, and subcellular localization. Here, after recapitulating the methods that have been employed in the discovery of proteins phosphorylated by Slt2, we review the bona fide substrates of this MAPK and the growing set of candidates still to be confirmed. In the context of the complexity of MAPK signaling regulation, we discuss how Slt2 determines yeast cell integrity through phosphorylation of these substrates. Increasing data from large-scale analyses and the available methodological approaches pave the road to early identification of new Slt2 substrates and functions.
芽殖酵母的细胞壁完整性（CWI）丝裂原活化蛋白激酶（MAPK）途径专门用于应对细胞壁损伤，但正在进行的研究表明，它参与许多其他应激条件，这表明它具有功能多样性。该途径的输出主要由MAPK Slt2的活性驱动，Slt2调节酵母生理学的重要过程，如通过CWI和其他途径对信号进行微调、响应细胞壁损伤的转录激活、细胞周期或某些细胞器命运的决定。为此，Slt2精确地磷酸化蛋白质底物，调节它们的活性、稳定性、蛋白质相互作用和亚细胞定位。在这里，在概述了用于发现被Slt2磷酸化的蛋白质的方法之后，我们回顾了这种MAPK的真正底物以及仍有待确认的越来越多的候选物。在MAPK信号调节复杂性的背景下，我们讨论Slt2如何通过这些底物的磷酸化来确定酵母细胞的完整性。来自大规模分析的越来越多的数据和可用的方法为早期鉴定新的Slt2底物和功能铺平了道路。
