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A phosphatase-centric mechanism drives stress signaling response
EMBO Reports ( IF 6.5 ) Pub Date : 2021-09-24 , DOI: 10.15252/embr.202152476
David Maria Hollenstein 1 , Gabriela Gérecová 1 , Natalie Romanov 2 , Jessica Ferrari 1 , Jiri Veis 1, 3 , Marion Janschitz 1 , Reinhard Beyer 4, 5 , Christoph Schüller 4, 5 , Egon Ogris 3 , Markus Hartl 1, 6 , Gustav Ammerer 1 , Wolfgang Reiter 1, 6
Affiliation  

Changing environmental cues lead to the adjustment of cellular physiology by phosphorylation signaling networks that typically center around kinases as active effectors and phosphatases as antagonistic elements. Here, we report a signaling mechanism that reverses this principle. Using the hyperosmotic stress response in Saccharomyces cerevisiae as a model system, we find that a phosphatase-driven mechanism causes induction of phosphorylation. The key activating step that triggers this phospho-proteomic response is the Endosulfine-mediated inhibition of protein phosphatase 2A-Cdc55 (PP2ACdc55), while we do not observe concurrent kinase activation. In fact, many of the stress-induced phosphorylation sites appear to be direct substrates of the phosphatase, rendering PP2ACdc55 the main downstream effector of a signaling response that operates in parallel and independent of the well-established kinase-centric stress signaling pathways. This response affects multiple cellular processes and is required for stress survival. Our results demonstrate how a phosphatase can assume the role of active downstream effectors during signaling and allow re-evaluating the impact of phosphatases on shaping the phosphorylome.

中文翻译:


以磷酸酶为中心的机制驱动应激信号反应



环境因素的变化会通过磷酸化信号网络导致细胞生理学的调整,该网络通常以激酶为活性效应子,以磷酸酶为拮抗元件。在这里,我们报告了一种逆转这一原理的信号机制。使用酿酒酵母的高渗应激反应作为模型系统,我们发现磷酸酶驱动的机制导致磷酸化的诱导。触发这种磷酸化蛋白质组学反应的关键激活步骤是硫磺介导的蛋白磷酸酶 2A-Cdc55 (PP2A Cdc55 ) 抑制,而我们没有观察到同时的激酶激活。事实上,许多应激诱导的磷酸化位点似乎是磷酸酶的直接底物,使 PP2A Cdc55成为信号转导反应的主要下游效应器,该信号转导反应平行且独立于已建立的以激酶为中心的应激信号转导通路。这种反应会影响多个细胞过程,并且是应激生存所必需的。我们的结果证明了磷酸酶如何在信号传导过程中发挥活性下游效应子的作用,并允许重新评估磷酸酶对塑造磷酰组的影响。
更新日期:2021-11-04
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