Abstract
Protein kinase A (PKA) is a cyclic AMP (cAMP)‐dependent protein kinase composed of catalytic and regulatory subunits and involved in various physiological phenomena, including lipid metabolism. In this study, we have investigated that the stoichiometric balance between catalytic and regulatory subunits is crucial to maintain basal PKA activity and lipid homeostasis. In Caenorhabditis elegans, suppression of PKA via RNAi resulted in severe phenotypes, including shortened lifespan, decreased egg laying, reduced locomotion, and altered lipid distribution. Similarly, in mammalian adipocytes, suppression of PKA regulatory subunits via siRNAs potently stimulated PKA activity, leading to potentiated lipolysis without increasing cAMP levels. Nevertheless, insulin exerted anti‐lipolytic effects and restored lipid droplet integrity by antagonizing PKA action. Together, these data implicate the importance of subunit stoichiometry as another regulatory mechanism of PKA activity and lipid metabolism.Support or Funding InformationThis work was supported by grants from the National Creative Research Initiative Program (2011‐0018312) funded by the Ministry of Education, Science and Technology. Y.J., J.S.H., J.K. were supported by BK21 program.
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