PHARMACOLOGY OF MAMMALIAN TARGET OF RAPAMYCIN (mTOR)

  Mammalian target of rapamycin (mTOR) is an evolutionally conserved serine/threonine kinase that integrates both intracellular and extracellular signals and serves as a central regulator of cell metabolism, growth, proliferation and survival. Interactions of mTOR with regulatory associated protein of TOR or rapamycin insensitive companion of mTOR result in two mTOR complexes, mTOR complex-1 and mTOR complex-2. Here we review several upstream and downstream regulators of mTOR complex-1 and mTOR complex-2. Upstream elements of the mTOR signaling pathway include Ras-homolog enriched in brain, and tuberous sclerosis complex 1 and 2, with tuberous sclerosis complex 2 as the linker between phosphatidylinositol 3-kinase/protein kinase B or Ras-Raf-mitogen-activated protein kinase extracellular signal-regulated protein kinase pathways and the mTOR pathway. Ribosomal protein S6 protein kinase 1 and eukaryotic initiation factor 4E binding protein 1 are currently the 2 best-known downstream effectors of mTOR complex-1 signaling; whereas serum and glucocorticoid induced protein kinase (SGK1) and serine threonine kinase (Akt) are downstream effectors of mTOR complex-2 signaling. Along with this we also discuss role of mTOR in various disease conditions like diabetes, obesity and cancer. Key words: mammalian target of rapamycin (mTOR), mTORC1, mTORC2, ribosomal S6 kinase 1 (S6K1)