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A phosphoproteomic approach reveals that PKD3 controls PKA-mediated glucose and tyrosine metabolism

ABSTRACT: Members of the Protein Kinase D (PKD) family (PKD1, 2, and 3) integrate hormonal and nutritional inputs to regulate complex cellular metabolism. Despite the fact that a number of functions have been annotated to particular PKDs, their molecular targets are relatively poorly explored. PKD3 promotes insulin sensitivity and suppresses lipogenesis in the liver of animals fed a high-fat diet. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified over three-hundred putative targets of PKD3. Further, biochemical analysis revealed that PKD3 regulates cAMP-dependent protein kinase A (PKA) activity, a master regulator of the hepatic response to glucagon and fasting. PKA regulates glucose, lipid, and amino acid metabolism in the liver, by targeting key enzymes in the respective processes. Among them the PKA targets phenylalanine hydroxylase (PAH) catalyzes the conversion of phenylalanine to tyrosine Consistently, we showed that PKD3 is activated by glucagon and promotes glucose and tyrosine levels in hepatocytes

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Fatty Liver Disease

SUBMITTER: Angel Loza Valdes

LAB HEAD: Grzegorz Sumara

PROVIDER: PXD026599 | Pride | 2021-06-17

REPOSITORIES: Pride

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