title: Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes.
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. Here we demonstrated that the stoichiometric balance between catalytic and regulatory subunits is crucial for maintaining basal PKA activity and lipid homeostasis. To uncover the potential roles of each PKA subunit, Caenorhabditis elegans was used to investigate the effects of PKA subunit deficiency. In worms, suppression of PKA via RNAi resulted in severe phenotypes, including shortened life span, decreased egg laying, reduced locomotion, and altered lipid distribution. Similarly, in mammalian adipocytes, suppression of PKA regulatory subunits RIα and RIIβ 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.
authors: From the Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, 08862 Seoul, Korea.
authors: Jung Hyun
authors: JH
authors: Lee
authors: From the Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, 08862 Seoul, Korea.
authors: Ji Seul
authors: JS
authors: Han
authors: From the Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, 08862 Seoul, Korea.
authors: Jinuk
authors: J
authors: Kong
authors: From the Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, 08862 Seoul, Korea.
authors: Yul
authors: Y
authors: Ji
authors: the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China and.
authors: Xuchao
authors: X
authors: Lv
authors: From the Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, 08862 Seoul, Korea, the Department of Biophysics and Chemical Biology, Seoul National University, Seoul 08862, Korea.
authors: Junho
authors: J
authors: Lee
authors: the MOE Key Laboratory of Bioinformatics and Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, 100084 Beijing, China and.
authors: Peng
authors: P
authors: Li
authors: From the Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, 08862 Seoul, Korea, jaebkim@snu.ac.kr.
authors: Jae Bum
authors: JB
authors: Kim
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / Q000235:genetics / Q000378:metabolism*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D051379:Mice
chemical_list: D029742:Caenorhabditis elegans Proteins; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit
keywords: adipose triglyceride lipase (ATGL); lipid droplet; lipolysis; protein kinase A (PKA); stoichiometry