2017-Cell-mTOR Signaling in Growth, Metabolism, and Disease

Figure 1. mTORC1 and mTORC2

(A) The mTORC1 and mTORC2 signaling pathways.
(B) mTORC1 subunits and respective binding sites on mTOR. The 5.9-A° cryo-EM structure of mTORC1 in complex with the FKBP12-rapamycin complex (without DEPTOR and PRAS40, PDB: 5FLC) is depicted as a space filling model and colored by subunit.
(C) mTORC2 subunits亚基 and respective binding sites结合位点 on mTOR.

Figure 2. The mTOR Signaling Network

(A) The signaling pathways upstream of mTORC1 and mTORC2. Positive regulators of mTORC1 signaling are shown in yellow, while negative regulators are shown in blue. mTORC1 and mTORC2 are shown in green and red, respectively.
(B) The major pathways downstream of mTORC1 signaling in mRNA translation, metabolism, and protein turnover.
(C) mTORC1 controls the activity of several transcription factors that can also be independently regulated by cell stress.
(D) The major pathways downstream of mTORC2 signaling response

Figure 3. Evolutionary Conservation of the TOR Pathway

(A) The nutrient sensing pathway 营养传感通道upstream of mammalian mTORC1 (left) and yeast TORC1 (right).
(B) Phylogenetic tree系统发生树 depicting the presence (green box) of key mTORC1 regulators in various model organisms.

Figure 4. Physiological Roles生理学功能 of mTOR

(A) mTORC1 controls the balance between anabolism合成代谢 and catabolism 分解代谢in response to fasting禁食 and feeding喂食.
(B) The effect of cumulative mTORC1 activity on overall health.
(C) The effect of mTORC1 hyperactivation超活化 in pancreatic胰腺 b cells on glucose tolerance over time.
(D) The normal functions of mTORC1 in the liver, muscle, pancreas胰腺, and adipose tissue脂肪组织 (left), and the consequences of chronic mTORC1 inhibition (middle) or activation (right).
(E) Deregulation of mTORC1 signaling in insulin resistance/diabetes糖尿病, and the effect of rapamycin or a theoretical mTORC1-specific inhibitor.
(F) Constitutive activation (red) and inhibition (purple) of mTORC1 signaling in the muscle leads to atrophy萎缩, whereas optimal muscle growth and function requires alternating periods of high and low mTORC1 activity (blue).

Figure 5. mTOR in Cancer and Aging

(A) The common tumor suppressors and oncogenes upstream of mTORC1 leading to increased mTORC1 signaling in a wide variety of cancers.
(B) The varying effects of rapalogs, catalytic mTOR inhibitors, or a combination of an mTOR inhibitor and autophagy inhibitor on cancer proliferation and survival.
(C) The role of mTORC1 signaling in aging.在卡路里限制或者Rapamycin的条件下可以延缓衰老的过程（负负得正）