Fig. 7. Calcineurin–NFAT signaling is interconnected with JNK signaling in vivo. (A) The dnJNK1/2 transgene was crossed with calcineurin Aβ gene-targeted mice to generate null mice (CnAβ–/–) or wild-type littermate controls (CnAβ+/+) for gravimetric analysis 1 week after TAC or sham operation. (N = 4–9 mice in each group; *P < 0.05 versus wild-type mice subjected to TAC; †P < 0.05 versus JNK1/2dn subjected to TAC). (B) Western for JNK1/2 protein from the hearts of MKK7–JNK1 fusion transgenic mice (upper band), wild-type mice, activated calcineurin transgenic mice or mice containing both the activated calcineurin and MKK7–JNK1 transgenes. The lower panel shows cJun kinase activity. (C) Analysis of wet ventricle-to-body weight ratios VW/BW from MKK7–JNK1 transgenic mice crossed with activated calcineurin transgenic mice (N = 4 mice in each group; *P < 0.05 versus WT; †P < 0.05 versus CnA transgenic. (D) Model whereby NFAT nuclear translocation and occupancy are controlled by the interplay between calcineurin-mediated dephosphorylation and kinase-mediated phosphorylation (left). Inhibition of a key NFAT kinase, such as JNK, shifts the equilibrium so that the same activation signal by calcineurin now results in greater NFAT translocation and nuclear occupancy.