title: AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum.
abstract: The beta-adrenergic receptor/cyclic AMP/protein kinase A (PKA) signalling pathway regulates heart rate and contractility. Here, we identified a supramolecular complex consisting of the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), its negative regulator phospholamban (PLN), the A-kinase anchoring protein AKAP18delta and PKA. We show that AKAP18delta acts as a scaffold that coordinates PKA phosphorylation of PLN and the adrenergic effect on Ca(2+) re-uptake. Inhibition of the compartmentalization of this cAMP signalling complex by specific molecular disruptors interferes with the phosphorylation of PLN. This prevents the subsequent release of PLN from SERCA2, thereby affecting the Ca(2+) re-uptake into the sarcoplasmic reticulum induced by adrenergic stimuli.
authors: Biotechnology Centre of Oslo, University of Oslo, PO Box 1125, Blindern, N-0317 Oslo, Norway.
authors: Birgitte
authors: B
authors: Lygren
authors: Cathrine Rein
authors: CR
authors: Carlson
authors: Katja
authors: K
authors: Santamaria
authors: Valentina
authors: V
authors: Lissandron
authors: Theresa
authors: T
authors: McSorley
authors: Jessica
authors: J
authors: Litzenberg
authors: Dorothea
authors: D
authors: Lorenz
authors: Burkhard
authors: B
authors: Wiesner
authors: Walter
authors: W
authors: Rosenthal
authors: Manuela
authors: M
authors: Zaccolo
authors: Kjetil
authors: K
authors: Taskén
authors: Enno
authors: E
authors: Klussmann
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism* / Q000648:ultrastructure; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D000099211:Phospholamban
chemical_list: D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D017868:Cyclic AMP-Dependent Protein Kinases; D008565:Membrane Proteins; D046912:Multiprotein Complexes; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban; C526078:Akap7 protein, rat; C506948:Atp2a2 protein, rat