BC020002 Activators

mTOR Activators comprise a diverse set of chemical compounds that either directly stimulate the kinase activity of mTOR or modulate various upstream pathways resulting in its activation. Key among these activators are insulin, amino acids, and glucose, which enhance mTOR activity through the PI3K/Akt and AMPK pathways. Insulin, by activating PI3K/Akt, leads to the inhibition of the TSC1/2 complex, liberating Rheb to activate mTOR. Similarly, amino acids, particularly leucine, directly engage the Rag GTPases, causing the translocation of mTOR to lysosomal membranes where it becomes fully active. Glucose bolsters mTOR activity by elevating ATP levels, thus inhibiting AMPK and, consequently, TSC1/2, culminating in mTOR activation. Growth factors such as EGF, PDGF, and IGF-1 also play crucial roles, with EGF and PDGF activating mTOR through the PI3K/Akt pathway via their respective receptors, and IGF-1 signaling through its receptor to inhibit TSC1/2, thereby activating mTOR.

Further enhancing the activity of mTOR are lipid-derived molecules like phosphatidicacid, oleic acid, palmitic acid, and eicosapentaenoic acid (EPA), which engage mTOR through distinct lipid signaling mechanisms. Phosphatidic acid binds to mTOR directly, enhancing its kinase activity, while oleic acid and palmitic acid alter cellular membrane composition, influencing mTOR localization and function. EPA impacts mTOR by modifying membrane fluidity, which affects signaling through receptor tyrosine kinases and the PI3K/Akt pathway. Additionally, compounds such as PAO and okadaic acid indirectly upregulate mTOR activity through inhibition of protein tyrosine phosphatases and serine/threonine phosphatases, respectively, leading to increased PI3K/Akt signaling and subsequent mTOR activation. Collectively, these mTOR Activators exert their effects through a network of signaling events that converge on mTOR, ensuring its activation and the promotion of its downstream cellular processes.