Figure 4: Examination of Ras/MAPK, CaMKII and CaN activity.
From: Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival
(a) Ras activity was significantly reduced in TBC1D10C TG vs. WT mice (after phenylephrine (PE) stimulation) (WT, uninjected: n = 4; WT + PE: n = 14; TG + PE: n = 15; P < 0.05; Student’s t-test), whereas (b) p-MEK1/2/t-MEK1/2 levels were not significantly diminished in PE stimulated TG vs. PE stimulated WT mice (WT, uninjected: n = 3; WT + PE: n = 15; TG, uninjected: n = 3; TG + PE: n = 15,n.s.; Student’s t-test). (c) Calcineurin (CaN) phosphatase activity was not different between WT and TG mice (n = 6 per group), suggesting CaN-independent signal pathways may be more important for the effects of TBC1D10C in vivo. (d) Mcip-1 (Modulatory calcineurin-interacting protein 1) mRNA expression, a marker for CaN activity, was not significantly changed in TG mice whereas (e) CaMKII (T286) phosphorylation was significantly diminished in TG mice (TG: n = 8; WT: n = 10; P < 0.01; Student’s t-test). Full length blots of the cropped membranes in Fig. 4b and e are displayed in Supplementary Figure 6.
