Xu et al. showed that in models of norepinephrine (NE)-induced cardiac hypertrophy, GDF-15 counteracts pathological growth responses not by Smad activation, but by interfering with epidermal growth factor receptor (EGFR) transactivation, a known downstream effect of G protein-coupled receptor (GPCR) signaling [102]. The gene discussed is EGFR; the disease is cardiac hypertrophy.