Fig. 1. Signal transduction pathways regulating fiber-type specific gene expression in skeletal muscle and activation of the hypertrophic gene expression program in both striated muscle types. In both tissues, prolonged Ca²⁺ transients, triggered by mechanical load, agonists or nerve activity among other signals, activate the phosphatase calcineurin, which controls nuclear accumulation of NFAT. NFAT together with GATA2 and GATA4 in skeletal and cardiac muscle, respectively, activate gene expression. MEF2 proteins are targets of an alternative signal transduction pathway mediated by CaM kinase (CaMK) and p38 MAPK. Cell-type-specific cofactors interact with MEF2 to activate the hypertrophic gene expression program independent of the calcineurin/NFAT pathway.