Figure 5
JNK2 activation mediates T3-stimulated cardiomyocyte proliferation in neonatal cardiomyocytes. (A) T3-stimulates ~54 kDa JNK phosphorylation, but not that of MKK4 and 7, indicating non-canonical activation of JNK by T3. (B) T3-stimulated c-Jun phosphorylation, the downstream effector of JNK activation and IGF-1 expression require JNK2. (C) Immunoprecipitation studies in lysates from neonatal cardiomyocytes show that T3 mainly phosphorylates the ~54 kDa JNK2α2 isoform (JNK2α2). In A–C, immunoblots are representative of 2 independent experiments. (D) Genetic Jnk2 deletion inhibits T3-stimulated cardiomyocyte proliferation but not developmental increases in cardiomyocyte numbers in neonates. Individual colors represent data from pups from unique litters. Jnk2 deletion also inhibits in vivo T3-stimulated IGF-1 expression in cardiomyocytes. Representative immunoblots of cardiomyocyte lysates are shown above the graph. In the latter experiment, T3 or vehicle treatment was given on P2 and the hearts harvested 12 h later for immunoblotting. *P < 0.05, ***P < 0.001, compared to WT littermates; n.s., nonsignificant. Error bars indicate SEM.
