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EMBO reports 8, 11, 1061–1067 (2007)
doi:10.1038/sj.embor.7401081
AOP Published online: 28 September 2007
AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum
Birgitte Lygren1*, Cathrine Rein Carlson1*, Katja Santamaria2, Valentina Lissandron3, Theresa McSorley2, Jessica Litzenberg2, Dorothea Lorenz2, Burkhard Wiesner2, Walter Rosenthal2, 4, Manuela Zaccolo3, Kjetil Taskén1 & Enno Klussmann2, 4
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1 Biotechnology Centre of Oslo, University of Oslo, PO Box 1125, Blindern, N-0317 Oslo, Norway
2 Leibniz-Institut fûr Molekulare Pharmakologie (FMP), D-13125 Berlin, Germany
3 Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, I-35124 Padova, Italy
4 Institut für Pharmakologie, Charité—Universitätsmedizin Berlin, Freie Universität Berlin, Campus Benjamin Franklin, 14195 Berlin, Germany
To whom correspondence should be addressed
Kjetil Taskén Tel: +47 22840505/0549; Fax: +47 22840506; E-mail: kjetil.tasken@biotek.uio.no
* These authors contributed equally to this work
Received 4 April 2007; Accepted 28 August 2007; Published online 28 September 2007.
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Abstract
The  -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 Ca2+-ATPase (SERCA2), its negative regulator phospholamban (PLN), the A-kinase anchoring protein AKAP18 and PKA. We show that AKAP18 acts as a scaffold that coordinates PKA phosphorylation of PLN and the adrenergic effect on Ca2+ 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 Ca2+ re-uptake into the sarcoplasmic reticulum induced by adrenergic stimuli.
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