Panel A. M-1 cells transduced with adenovirus expressing Nedd4-2, Nedd4-2ΔC2, Nedd4-2ΔWW2,3 or empty virus and Isc measured in Ussing chambers under control conditions and after treatment with 100 nM dexamethasone (dex) for 24 hr. M-1 cells overexpressing all 3 isoforms had significantly lower currents as compared to empty virus (**P < 0.001; Tukey’s pairwise multiple comparison, SigmaStat; n = 15; mean ± SE). Following steroid treatment, currents were significantly different in between each of the Nedd4-2 isoforms (## P < 0.001 compared to Nedd4-2ΔWW2,3; $P < 0.05 compared to Nedd4-2ΔWW2,3; ¶P < 0.05 compared to Nedd4-2; Tukey’s pairwise multiple comparison, SigmaStat; n = 15; mean ± SE). Panel B. Representative western blot of transduced M-1 cells demonstrate relatively equal expression of each of the Nedd4-2 isoforms. Full length Nedd4-2 migrates at ~116 kDa; Nedd4-2ΔC2 (N4-2ΔC2) migrates at ~101 kDa and Nedd4-2ΔWW2,3 (N4-2ΔWW2,3) migrates at ~83 kDa.