Cardiac myocyte growth is under differential control of mammalian target of rapamycin (mTOR) and glycogen-synthase-kinase-3beta (GSK3beta). Whereas active GSK3beta negatively regulates growth and down-regulates cellular protein synthesis, activation of the mTOR pathway promotes protein expression and cell growth. Here we report that depletion of mTOR via siRNA mediated knockdown causes marked down-regulation of GSK3beta protein in cardiac myocytes. As a result, GSK3beta target protein beta-catenin becomes stabilized and translocates into the nucleus. Moreover, mTOR knockdown leads to increase in cardiac myocyte surface area and produces an up-regulation of the fetal gene program. Our findings suggest a new type of convergence of mTOR and GSK3beta activities, indicating that GSK3beta-dependent stabilization of beta-catenin in cardiac myocytes is influenced by mTOR.