Figure 7.

The proposed mechanism of DKK3 regulation of cardiac hypertrophy. On the basis of our in vitro and in vivo data, we propose that DKK3 physically interacts with ASK1 to inhibit ASK1 activity under normal conditions (left panel). Under conditions of aortic banding or other hypertrophic stress, DKK3 is down-regulated and dissociates from ASK1 (right panel); as a result, ASK1 is phosphorylated and activates MKK4/7 and MKK3/6, which then sequentially phosphorylate downstream JNK1/2 and P38, which activate multiple transcription factors that relate to cardiac hypertrophy.