An Overview of the mTOR Pathway
The mTOR Pathway
Introduction
The mammalian target of rapamycin (mTOR) signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation and survival. Discoveries that have been made over the last decade show that the mTOR pathway is activated during various cellular processes (e.g. tumor formation, insulin resistance, adipogenesis and T-lymphocyte activation) and is deregulated in human diseases such as cancer and type 2 diabetes (Laplante et al., 2009). These observations have attracted broad scientific and clinical interest in the mTOR pathway. This is highlighted by the growing use of mTOR inhibitors [rapamycin and its analogues (rapalogues)] in pathological settings, including the treatment of solid tumors, organ transplantation, and rheumatoid arthritis (Laplante et al., 2009). mTOR nucleates at least two distinct multi-protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Here, I will highlight and summarize the current understanding of how the mTOR pathway affects cell metabolism, growth, proliferation and survival.
BackGround
mTORC1 mTORC1 has five components: mTOR, which is the catalytic subunit of the complex; regulatory-associated protein of mTOR (Raptor); mammalian lethal with Sec13 protein 8 (mLST8, also known as GβL); proline-rich AKT substrate 40 kDa (PRAS40); and DEP-domain-containing mTOR-interacting protein (Deptor) (Peterson et al., 2009). The exact function of most of the mTOR-interacting proteins in mTORC1 still remains elusive. It has been proposed that Raptor might affect mTORC1 activity by regulating assembly of the complex and by recruiting substrates for mTOR (Peterson et al., 2009). The role of mLST8 in mTORC1 function is also unclear, as deletion of this protein does not affect mTORC1 activity in vivo (Wang et al., 2007). PRAS40 and Deptor have been characterized as distinct negative regulators of mTORC1 (Peterson et al.,
Introduction
The mammalian target of rapamycin (mTOR) signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation and survival. Discoveries that have been made over the last decade show that the mTOR pathway is activated during various cellular processes (e.g. tumor formation, insulin resistance, adipogenesis and T-lymphocyte activation) and is deregulated in human diseases such as cancer and type 2 diabetes (Laplante et al., 2009). These observations have attracted broad scientific and clinical interest in the mTOR pathway. This is highlighted by the growing use of mTOR inhibitors [rapamycin and its analogues (rapalogues)] in pathological settings, including the treatment of solid tumors, organ transplantation, and rheumatoid arthritis (Laplante et al., 2009). mTOR nucleates at least two distinct multi-protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Here, I will highlight and summarize the current understanding of how the mTOR pathway affects cell metabolism, growth, proliferation and survival.
BackGround
mTORC1 mTORC1 has five components: mTOR, which is the catalytic subunit of the complex; regulatory-associated protein of mTOR (Raptor); mammalian lethal with Sec13 protein 8 (mLST8, also known as GβL); proline-rich AKT substrate 40 kDa (PRAS40); and DEP-domain-containing mTOR-interacting protein (Deptor) (Peterson et al., 2009). The exact function of most of the mTOR-interacting proteins in mTORC1 still remains elusive. It has been proposed that Raptor might affect mTORC1 activity by regulating assembly of the complex and by recruiting substrates for mTOR (Peterson et al., 2009). The role of mLST8 in mTORC1 function is also unclear, as deletion of this protein does not affect mTORC1 activity in vivo (Wang et al., 2007). PRAS40 and Deptor have been characterized as distinct negative regulators of mTORC1 (Peterson et al.,