Figure 2.

Abbreviated diagrammatic representation of the PI3K, Akt, mTOR cell signaling pathway, and associated pathways, as a major regulator of cell function (see Laplante and Sabatini¹¹ for a more extensive chart of mTOR-related cell signaling). The mTOR is an atypical serine/threonine kinase that is present in 2 distinct complexes. The first, mTORC1, is highlighted and is composed of mTOR, Raptor, GβL, and DEPTOR and is inhibited by rapamycin. It is a master growth regulator that senses and integrates diverse nutritional and environmental cues, including growth factors, energy levels, cellular stress, and amino acids. It couples these signals to the promotion of cellular growth by phosphorylating substrates that potentiate anabolic processes such as mRNA translation and lipid synthesis or limit catabolic processes such as autophagy. The pathways from mTORC1 leading to activation of autophagy (highlighted) are indicated in red (heavy arrows). Interactions with AMPK (circled) are also shown. Overactivity of mTORC1 is believed to trigger inflammatory processes which can result in pathological injury and processes leading to many cancers and degenerative diseases; and aberrant mTOR signaling is involved in many disease states including cancer, cardiovascular disease, and diabetes. Adapted from Moore¹² and with permission from Cell Signaling Technology, mTOR Signaling Interactive Pathway: https://www.cellsignal.com/contents/science-cst-pathways-pi3k-akt-signaling-resources/mtor-signaling-interactive-pathway/pathways-mtor-signaling. Key to major constituents and symbols: Akt indicates serine/threonine kinase or protein kinase B; AMPK, 5′-adenosine monophosphate-activated protein kinase; mRNA, messenger RNA; mTOR, mechanistic target of rapamycin; mTORC1, mammalian target of rapamycin complex 1; PI3K, phosphatidylinositol-3 kinase; PIP₃, phosphatidylinositol 3,4,5 trisphosphate; PTEN, phosphatase and tensin homolog; ROS, reactive oxygen species; activation, ↑; inhibition, T.