Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress

Abstract

The large serine/threonine protein kinase mTOR regulates cellular and organismal homeostasis by coordinating anabolic and catabolic processes with nutrient, energy, and oxygen availability and growth factor signaling. Cells and organisms experience a wide variety of insults that perturb the homeostatic systems governed by mTOR and therefore require appropriate stress responses to allow cells to continue to function. Stress can manifest from an excess or lack of upstream signals or as a result of genetic perturbations in upstream effectors of the pathway. mTOR nucleates two large protein complexes that are important nodes in the pathways that help buffer cells from stresses, and are implicated in the progression of stress-associated phenotypes and diseases, such as aging, tumorigenesis, and diabetes. This review focuses on the key components of the mTOR complex 1 pathway and on how various stresses impinge upon them.

Figure 1

Growth factors activate mTORC1 through multiple pathways. Black lines signify activating connections, whereas red lines signify inhibitory inputs between proteins. Dotted lines indicate connections between proteins that are not known to be direct.

Figure 2

A variety of stresses regulate mTORC1 through multiple pathways. Black lines signify activating connections, whereas red lines signify inhibitory inputs between proteins. Dotted lines indicate connections between proteins that are not known to be direct.