A phosphatase‐centric mechanism drives stress signaling response. (24th September 2021)

• Record Type: Journal Article
• Authors: Hollenstein, David Maria; Gérecová, Gabriela; Romanov, Natalie; Ferrari, Jessica; Veis, Jiri; Janschitz, Marion; Beyer, Reinhard; Schüller, Christoph; Ogris, Egon; Hartl, Markus; Ammerer, Gustav; Reiter, Wolfgang
• Is Part Of: EMBO reports. Volume 22:Number 11(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-24
• Subjects: endosulfine -- greatwall kinase -- hyperosmotic stress signaling -- phosphatase -- PP2A; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.202152476
• Languages: English
• ISSNs: 1469-221X

Abstract

Abstract: 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 (PP2A Cdc55 ), 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 PP2A Cdc55 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. Synopsis: The phosphatase PP2A Cdc55 assumes the role of an active downstream effector during hyperosmotic stress signaling in Saccharomyces cerevisiae . Inhibition of the phosphatase is the key event resulting in increased phosphorylation, while induction of kinases affecting the same substrates appears not to be required. Greatwall kinase‐Endosulfine‐PP2A pathway regulates hyperosmotic stress signaling. Stress‐induced inhibition of PP2A Cdc55 is sufficient to promote phosphorylation of proline directed phosphorylation motifs. Abstract : The phosphatase PP2A Cdc55 assumes the role of an active downstream effector during hyperosmotic stress signaling in Saccharomyces cerevisiae . Inhibition of the phosphatase is the key event resulting in increased phosphorylation, while induction of kinases affecting the same substrates appears not to be required.