An Asymmetrically Balanced Organization of Kinases versus Phosphatases across Eukaryotes Determines Their Distinct Impacts

• DOI: 10.1371/journal.pcbi.1005221
• Publication Date: 2017-01-30T18:34:13Z
• Authors: Ilan Smoly; Netta Shemesh; Michal Ziv-Ukelson; Anat Ben-Zvi; Esti Yeger-Lotem
• Keywords: Phosphoproteomics

Protein phosphorylation underlies cellular response pathways across eukaryotes and is governed by the opposing actions of phosphorylating kinases de-phosphorylating phosphatases. While phosphatases have been extensively studied, their organization mechanisms which they balance each other are not well understood. To address these questions we performed quantitative analyses large-scale 'omics' datasets from yeast, fly, plant, mouse human. We uncovered an asymmetric a previously-hidden scale: Each organism contained many different kinase genes, were balanced small set highly abundant phosphatase proteins. Kinases much more responsive to perturbations at gene protein levels. In addition, had diverse scales phenotypic impact when manipulated. Phosphatases, in contrast, stable, robust flatly organized, with rather uniform downstream. validated aspects this experimentally nematode, supported additional theoretic analysis dynamics phosphorylation. Our explain empirical bias field toward characterization therapeutic targeting expense show quantitatively broadly that only historical bias, but stems wide-ranging differences impact. The between regulators also common two post-translational modification systems, suggesting its fundamental value.