Fig. 6

Schematic diagram of AC6 and AC6-ΔN signaling. The AC6 signaling pathway in a WT cardiomyocyte (AC6^+/+) is shown in the upper panel. AC6 normally anchors on the sarcolemmal membrane and interacts with AKAP and PKA. The lower panel shows the signaling pathway in a cardiomyocyte (AC6^ΔN/ΔN) that expresses AC6-ΔN (an AC6 variant that lacks aa 2–86), but not the full-length AC6. Our data suggest that AC6-ΔN re-distributes from the sarcolemmal membrane to the sarcoplasmic reticulum (SR), indicating a role of AC6-N in the anchorage of AC6 on the sarcolemmal membrane. Our data also suggest that AC6 locates on the sarcolemmal membrane, and allows the PKA/Src/STAT3 pathway to be activated by β adrenergic receptors (β-ARs). While the AC6-ΔN variant is redistributed to SR, the AC6/PKA/Src/STAT3 pathway is unable to be activated during cardiac stress, and consequently results in poor survival of cardiac myocytes