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Multi-omics analysis identifies drivers of protein phosphorylation
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Journal Article
Multi-omics analysis identifies drivers of protein phosphorylation
2023
Overview
Background
Phosphorylation of proteins is a key step in the regulation of many cellular processes including activation of enzymes and signaling cascades. The abundance of a phosphorylated peptide (phosphopeptide) is determined by the abundance of its parent protein and the proportion of target sites that are phosphorylated.
Results
We quantified phosphopeptides, proteins, and transcripts in heart, liver, and kidney tissue samples of mice from 58 strains of the Collaborative Cross strain panel. We mapped ~700 phosphorylation quantitative trait loci (phQTL) across the three tissues and applied genetic mediation analysis to identify causal drivers of phosphorylation. We identified kinases, phosphatases, cytokines, and other factors, including both known and potentially novel interactions between target proteins and genes that regulate site-specific phosphorylation. Our analysis highlights multiple targets of pyruvate dehydrogenase kinase 1 (PDK1), a regulator of mitochondrial function that shows reduced activity in the NZO/HILtJ mouse, a polygenic model of obesity and type 2 diabetes.
Conclusions
Together, this integrative multi-omics analysis in genetically diverse CC strains provides a powerful tool to identify regulators of protein phosphorylation. The data generated in this study provides a resource for further exploration.
Publisher
BioMed Central,Springer Nature B.V,BMC
Subject
/ Animals
/ Biomedical and Life Sciences
/ Diabetes mellitus (non-insulin dependent)
/ Diabetes Mellitus, Type 2 - genetics
/ genome
/ Genomes
/ Heart
/ Kidneys
/ Kinases
/ Liver
/ Males
/ Mice
/ Microbial Genetics and Genomics
/ noninsulin-dependent diabetes mellitus
/ obesity
/ Peptides
/ Proteins
/ pyruvate dehydrogenase (acetyl-transferring) kinase
