ERK pathway inhibition by U0126 leads to CaMKII activation and triggers the AKT/CREB pathway in the spinal cord of SMA-like mice. A–D, Western blot analysis and quantification of AKT protein in the ventral lumbar spinal cord of vehicle- and U0126-treated control mice at 2 and 6 d of age, vehicle-treated SMA-like mice at 2 d of age, and U0126-treated SMA-like mice at 2 and 6 d of age (A, B) (n = 3) and in vehicle- and U0126-treated human SMA cultured myotubes from two type 2 SMA patients (C, D) (n = 3). E, F, Western blot analysis and quantification of CREB protein phosphorylation in the ventral lumbar spinal cord of control mice at 6 d of age and SMA-like mice at 2 d of age, treated by vehicle, ERK inhibitor U0126 with or without CaMKII inhibitor KN-93 (n = 3). G–J, Kinetic analysis by Western blot of CaMKII protein activation (G), AKT protein activation (H), and CREB protein activation (I) after in vivo ERK inhibition by U0126 in spinal cords of control mice at 6 d of age and quantifications (n = 2) (J). K–N, Kinetic analysis by Western blot of CaMKII protein activation (K), AKT protein activation (L), and CREB protein activation (M) after in vivo ERK inhibition by U0126 in spinal cords of SMA-like mice at 2 d of age and quantifications (n = 2) (N). Data are displayed as mean ± SEM. *p < 0.05.