Global Phosphoproteomic Analysis Reveals Significant Metabolic Reprogramming in the Termination of Liver Regeneration in Mice

Phosphorylation is crucial in regulating various biological processes. However, comprehensive phosphoproteomic profiling in the termination of liver regeneration (LR) is still missing. Here, we used TMT labeling coupled with phosphopeptides enrichment and 2D LC-MS/MS analysis to establish a global phosphoproteomic map in the liver of mice at day 5 after partial hepatectomy (PH). Altogether, 9731 phosphosites from 3443 proteins were identified and 7802 phosphosites from 2980 proteins were quantified. Motif analysis of the identified phosphosites revealed a diverse array of consensus sequences, suggesting multiple kinase families including ERK/MAPK, PKA/PKC, CaMK-II, CKII and CDK may be involved in the termination of LR. Functional clustering analysis of proteins with dysregulated phosphosites showed that they mainly participate in metabolic pathways, DNA replication and tight junction. More importantly, deletion of PP2Acα in the liver remarkably changes the overall phosphorylation profile, indicating its c...