Investigation of Proteomic and Phosphoproteomic Responses to Signaling Network Perturbations Reveals Functional Pathway Organizations in Yeast

摘要

Governance of protein phosphorylation by kinasesand phosphatases constitutes an essential regulatorynetwork in eukaryotic cells. Network dysregulationleads to severe consequences and is often a key factorin disease pathogenesis. Previous studies revealedmultiple roles for protein phosphorylationand pathway structures in cellular functions fromdifferent perspectives. We seek to understand theroles of kinases and phosphatases from a protein homeostasispoint of view. Using a streamlined tandemmass tag (SL-TMT) strategy, we systematically measureproteomic and phosphoproteomic responses toperturbations of phosphorylation signaling networksin yeast deletion strains. Our results emphasize therequirement for protein normalization for more completeinterpretation of phosphorylation data. Functionalrelationships between kinases and phosphataseswere characterized at both proteome andphosphoproteome levels in three ways: (1) GeneOntology enrichment analysis, (2) Dgene-Dgene correlationnetworks, and (3) molecule covariance networks.This resource illuminates kinase and phosphatasefunctions and pathway organizations.