Figure 4.

JNK2 increases SERCA2-ATPase activity in a CaMKII-independent manner. A) Summarized data showing active purified human JNK2 (hJNK2) proteins increase thapsigargin-sensitive SERCA2-ATPase activity in isolated human SR vesicles, but additional treatment of CaMKII inhibitor KN93 (1 μM) has no inhibitory effect on this JNK2-enhanced SERCA2-ATPase activity. B) Pooled data of elevated [Ca²⁺]_SR load in 0.23% alcohol (Alc)-exposed (24 hr) HL-1 myocytes with the treatment of CaMKII inhibitor KN93 compared to sham controls (sham) and positive controls treated with KN92 (an inactive analogue of KN93), suggesting lack of action of CaMKII on alcohol-elevated load. C) Summarized data showing CaMKII inhibition has no effect on 50 nM anisomycin (Aniso)-induced increase of [Ca²⁺]_SR load in KN93+Aniso treated as well as KN92+Aniso treated HL-1 myocytes compared to sham controls (sham). D) Summarized data of [Ca²⁺]_SR load in isolated myocytes from alcohol-exposed PLNKO mice showing an increase in [Ca²⁺]_SR load compared to vehicle-treated PLNKO sham controls and JNK2 inhibitor JNK2I treatment precluded this alcohol-evoked increase of [Ca²⁺]_SR load, while lack of PLB in PLNKO mice (vehicle-treated sham controls) markedly increases [Ca²⁺]_SR load compared to WT littermate controls. E) Pooled data of Ca²⁺-dependent curves of SERCA2-ATPase activity in anti-PLB antibody 2D12 (6 ug) pre-treated human atrial SR vesicles incubated with (pink) and without (blue) pure active hJNK2 (64 ng) compared to sham controls (black).