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Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes.

J Biol Chem. 2016 Sep 23;291(39):20315-28. Epub 2016 Aug 04
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摘要


Protein kinase A is a cyclic AMP (cAMP)-dependent protein kinase composed of catalytic and regulatory subunits and involved in various physiological phenomena, including lipid metabolism. Here we demonstrated that the stoichiometric balance between catalytic and regulatory subunits is crucial for maintaining basal activity and lipid homeostasis. To uncover the potential roles of each duanyu1529 subunit, Caenorhabditis elegans was used to investigate the effects of duanyu1529 subunit deficiency. In worms, suppression of duanyu1529 via resulted in severe phenotypes, including shortened life span, decreased egg laying, reduced locomotion, and altered lipid distribution. Similarly, in mammalian adipocytes, suppression of duanyu1529 regulatory subunits RIα and RIIβ via siRNAs potently stimulated duanyu1529 activity, leading to potentiated lipolysis without increasing cAMP levels. Nevertheless, insulin exerted anti-lipolytic effects and restored lipid droplet integrity by antagonizing duanyu1529 action. Together, these data implicate the importance of subunit stoichiometry as another regulatory mechanism of duanyu1529 activity and lipid metabolism.

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