AktmTOR

AktmTOR, also known as mTORC1, is a multiprotein complex that plays a crucial role in regulating cell growth, proliferation, and metabolism. It is a central integrator of nutrient and growth factor signals, controlling protein synthesis, lipid synthesis, and autophagy. The complex consists of the mammalian target of rapamycin (mTOR) kinase and several associated proteins, including Raptor, PRAS40, mLST8, and Deptor.

AktmTOR is activated by growth factors, amino acids, and energy status, all of which are sensed by the cell. Growth factors typically activate Akt, which then phosphorylates and inhibits TSC2, a component of the TSC1/TSC2 complex. This inhibition relieves the suppression of Rheb, a small GTPase that directly activates AktmTOR. Amino acids also activate AktmTOR, primarily through a pathway involving the Rag GTPases. Energy status, monitored by AMP-activated protein kinase (AMPK), can inhibit AktmTOR when energy levels are low.

Once activated, AktmTOR phosphorylates downstream targets that promote anabolic processes. A key target is S6 kinase (S6K), which in turn phosphorylates the ribosomal protein S6, enhancing translation initiation and elongation. AktmTOR also phosphorylates the eukaryotic translation initiation factor 4E-binding protein (4E-BP), releasing eIF4E and promoting cap-dependent translation. Furthermore, AktmTOR promotes lipid synthesis by activating sterol regulatory element-binding proteins (SREBPs).

Dysregulation of AktmTOR signaling is implicated in various diseases, including cancer, diabetes, and neurodegenerative disorders. In cancer, AktmTOR is often hyperactivated, contributing to uncontrolled cell proliferation and tumor growth. Inhibitors of AktmTOR, such as rapamycin and its analogs, are used as immunosuppressants and have shown promise in cancer therapy.