mTOR Substrate Phosphorylation in Growth Control: An Update

Background: The mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine protein kinase that integrates inputs on nutrient status, energy levels, and growth factor stimulation to accordingly regulate cell growth and metabolism. It does this by activating or repressing target proteins covering a broad array of cellular processes. mTOR nucleates two structurally and functionally distinct protein complexes, mTORC1 and mTORC2. Because of their wide-ranging effects in the cell, both mTOR complexes are presumed to have a large number of targets. However, only a relatively small number have been conclusively identified. Methods: With emphasis on mammalian mTOR, we previously reviewed the extensive mTOR literature (1991-2021) and compiled a list of all reported substrates of mTORC1 and mTORC2. We have updated this list for the period 2022-2025. Results/Conclusions: Many of the targets are involved in autophagy, underscoring the major role of mTOR in the regulation of this process. From the perspective of this Special Issue, targets linked to cancer may be responsible for executing an mTOR-driven pro-oncogenic program and merit future study.