Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy.

Phospholamban (PLN) plays a central role in Ca homeostasis in cardiac myocytes through regulation of the sarco(endo)plasmic reticulum Ca-ATPase 2A (SERCA2A) Ca pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in humans and transgenic mice, but the downstream signaling defects leading to decompensation and heart failure are poorly understood. Here we used precision mass spectrometry to study the global phosphorylation dynamics of 1,887 cardiac phosphoproteins in early affected heart tissue in a transgenic R9C mouse model of DCM compared with wild-type littermates.