RT Journal Article
SR Electronic
T1 A phosphoproteomic approach reveals that PKD3 controls phenylalanine and tyrosine metabolism
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.20.211474
DO 10.1101/2020.07.20.211474
A1 Alexander E. Mayer
A1 Angel Loza-Valdes
A1 Werner Schmitz
A1 Jonathan Trujillo Viera
A1 Michael Leitges
A1 Andreas Schlosser
A1 Grzegorz Sumara
YR 2020
UL http://biorxiv.org/content/early/2020/07/22/2020.07.20.211474.abstract
AB 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. However, its substrates are largely unknown. Here we applied proteomic approaches to determine PKD3 targets. We identified over three-hundred putative targets of PKD3. Among them phenylalanine hydroxylase (PAH). PAH catalyses the conversion of phenylalanine to tyrosine and its activity is regulated by, phenylalanine concentration and glucagon-induced signaling. Consistently, we showed that PKD3 is activated by glucagon and promotes tyrosine levels in primary hepatocytes and liver of mice.Taken together, our comprehensive proteomic approach established that PKD3 determine the rate of phenylalanine to tyrosine conversion in the liver. Therefore, our data indicate that PKD3 might play a role in development of diseases related to the defective tyrosine and phenylalanine metabolism.