RT Journal Article
SR Electronic
T1 Multi-omics analysis identifies drivers of protein phosphorylation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.06.03.494740
DO 10.1101/2022.06.03.494740
A1 Tian Zhang
A1 Gregory R. Keele
A1 Isabela Gerdes Gyuricza
A1 Matthew Vincent
A1 Catherine Brunton
A1 Timothy A. Bell
A1 Pablo Hock
A1 Ginger D. Shaw
A1 Steven C. Munger
A1 Fernando Pardo-Manuel de Villena
A1 Martin T. Ferris
A1 Joao A. Paulo
A1 Steven P. Gygi
A1 Gary A. Churchill
YR 2022
UL http://biorxiv.org/content/early/2022/12/08/2022.06.03.494740.abstract
AB 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. 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.Competing Interest StatementThe authors have declared no competing interest.