Pleiotropic roles of mTOR complexes in haemato-lymphopoiesis and leukemogenesis.

Abstract

Mammalian/mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that responds to environmental determinants such as growth factor concentration, nutrient availability, energy sufficiency and stress. mTOR forms two different complexes, called mTOR complex 1 (mTORC1) and mTORC2, and these complexes have distinct substrate molecules that function in the regulation of protein translation and cellular metabolism. Although mTOR was originally discovered as a target protein of rapamycin, a natural macrolide immunosuppressant, rapamycin mainly inhibits the kinase activity of mTORC1, whereas mTORC2 is affected to a much lesser extent. The inhibitory effects of rapamycin on mTORC1 substrates are complex, and the use of rapamycin to investigate mTORC functions may provide misleading results. In contrast to pharmacological inhibition, studies using genetic approaches to the disruption of mTORC subunits have clearly demonstrated the physiological roles of the distinct mTOR complexes in organogenesis and tumourigenesis. In this review, we provide an overview of current knowledge about the roles of the mTOR complexes in haemato-lymphopoiesis and leukemogenesis.