CLK4 and cardiac hypertrophy: On the one hand, cardiomyocytes overexpressing Clk4 were resistant to phenylephrine (PE)-induced hypertrophy, which was rescued by simultaneous knockdown of Nexn. On the other hand, overexpression of a phosphorylation-mimic mutant of NEXN (S437E) but not wild-type NEXN or a phosphorylation-null mutant of NEXN (S437A) inhibited Clk4 knockdown-induced cardiac hypertrophy (Fig. 5a, b).