Djouder, NabilTuerk, Roland DSuter, MarianneSalvioni, PaoloThali, Ramon FScholz, RolandVaahtomeri, KariAuchli, YolandaRechsteiner, HeleneBrunisholz, René AViollet, BenoitMäkelä, Tomi PWallimann, TheoNeumann, DietbertKrek, Wilhelm2024-02-082024-02-082010-01-20EMBO J . 2010 ;29(2):469-81.http://hdl.handle.net/20.500.12105/17542The mobilization of metabolic energy from adipocytes depends on a tightly regulated balance between hydrolysis and resynthesis of triacylglycerides (TAGs). Hydrolysis is stimulated by beta-adrenergic signalling to PKA that mediates phosphorylation of lipolytic enzymes, including hormone-sensitive lipase (HSL). TAG resynthesis is associated with high-energy consumption, which when inordinate, leads to increased AMPK activity that acts to restrain hydrolysis of TAGs by inhibiting PKA-mediated activation of HSL. Here, we report that in primary mouse adipocytes, PKA associates with and phosphorylates AMPKalpha1 at Ser-173 to impede threonine (Thr-172) phosphorylation and thus activation of AMPKalpha1 by LKB1 in response to lipolytic signals. Activation of AMPKalpha1 by LKB1 is also blocked by PKA-mediated phosphorylation of AMPKalpha1 in vitro. Functional analysis of an AMPKalpha1 species carrying a non-phosphorylatable mutation at Ser-173 revealed a critical function of this phosphorylation for efficient release of free fatty acids and glycerol in response to PKA-activating signals. These results suggest a new mechanism of negative regulation of AMPK activity by PKA that is important for converting a lipolytic signal into an effective lipolytic response.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/LipolysisAMP-Activated Protein KinasesAdipocytesAdrenergic beta-AgonistsAnimalsCells, CulturedCyclic AMP-Dependent Protein KinasesFatty AcidsGlycerolIsoproterenolMicePhosphorylationPoint MutationProtein Serine-Threonine KinasesProtein SubunitsAttribution-NonCommercial-NoDerivatives 4.0 Internacional1994285929246910.1038/emboj.2009.3391460-2075The EMBO journalopen access