AKAP complex regulates Ca2+ re-uptake into heart sarcoplasmic reticulum

作者：Lygren Birgitte; Carlson Cathrine Rein; Santamaria Katja; Lissandron Valentina; McSorley Theresa; Litzenberg Jessica; Lorenz Dorothea; Wiesner Burkhard; Rosenthal Walter; Zaccolo Manuela; Tasken Kjetil^*; Klussmann Enno

来源：EMBO Reports, 2007, 8(11): 1061-1067.

DOI：10.1038/sj.embor.7401081

• cAMP
• calcium
• heart
• phospholamban
• AKAP

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 Ca2+ - ATPase ( SERCA2), its negative regulator phospholamban ( PLN), the A- kinase anchoring protein AKAP18 delta and PKA. We show that AKAP18 delta 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.

• 出版日期2007-11