Figure 1

Insulin mammalian target of rapamycin signaling pathways. Insulin activates mTORC1 through phosphoinositide 3 kinase (PI 3-K)/Akt mediated pathways. mTORC1 consists of the regulatory-associated protein of mTOR (Raptor), the proline rich Akt substrate 40 kDa (PRAS40), the mammalian lethal with Sec13 protein 8 (mLST8), and the DEP domain-containing mTOR interacting protein (Deptor). Insulin can stimulate PI 3-K activation and subsequent recruitment of Akt to the plasma membrane through activation by phosphoinositide dependent kinase 1 (PDK1). Once active, Akt can result in the activation of mTORC1 through a series of signaling pathways. Akt can also directly phosphorylate PRAS40 and reduce its binding to Raptor and release mTORC1 from its suppression by PRAS40. Upon activation, mTORC1 phosphorylates its two major downstream targets p70 ribosome S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1) and mediates cell growth, proliferation, and cell survival. mTOR can lead to inhibitory phosphorylation of the insulin receptor substrate 1 (IRS1). mTORC2 contains Rictor, mTOR, mLST8, Deptor, the mammalian stress-activated protein kinase interacting protein (mSIN1), and protein observed with Rictor-1 (Protor-1). The sirtuin SIRT1 may regulate the transcription of the gene encoding rapamycin insensitive companion of mTOR (Rictor) and promote the activation of mTORC2. mTORC2 regulates actin skeleton organization and cell survival through activating Akt and protein kinase C (PKC). In addition, mTORC2 can activate Rho GTPases and control cell to cell contact via Rho signaling pathways.