RRC ID 53310
著者 Lee JH, Han JS, Kong J, Ji Y, Lv X, Lee J, Li P, Kim JB.
タイトル Protein Kinase A Subunit Balance Regulates Lipid Metabolism in Caenorhabditis elegans and Mammalian Adipocytes.
ジャーナル J Biol Chem
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.
巻・号 291(39)
ページ 20315-28
公開日 2016-9-23
DOI 10.1074/jbc.M116.740464
PII S0021-9258(20)35910-X
PMID 27496951
PMC PMC5034032
MeSH 3T3-L1 Cells Animals Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / genetics Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit / metabolism* Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / metabolism* Lipid Metabolism / physiology* Mice
IF 4.238
引用数 9
リソース情報
線虫 tm635