mTORC2: the other facet of mTOR

Abstract

Publisher Summary This chapter provides an overview of the structure, function, and regulation of mammalian target of rapamycin complex 2 (mTORC2). It also discusses its potential as a target for drug development. The TOR protein was first discovered in the early 1990s in the budding yeast Saccharomyces cerevisiae as the gene product in which mutations confer resistance to the growth inhibitory properties of the macrocyclic lactone, rapamycin. Soon after, TOR was identified and cloned in mammalian cells. TOR is a highly conserved serine/threonine kinase, which is a major regulator of cell growth, proliferation, survival, and metabolism in all eukaryotes. Higher eukaryotes have only a single TOR gene, unlike budding and fission yeast that contain two TOR genes suggesting the existence of two separate TOR signaling axes. The existence of these two signaling networks have been subsequently demonstrated by the identification of two structurally and functionally distinct multiprotein complexes in yeast (TOR Complex 1 and TOR Complex 2) and in mammals (mTORC1 and mTORC2), in which TOR (or mTOR) is the core component. These complexes contain shared and distinct partners and control many cellular processes in response to diverse environmental cues.