mTOR signaling pathway

The mammalian target of rapamycin, mTOR, is a serine/threonine protein kinase that plays a crucial role in the nutrient-sensitive signaling pathway that regulates cell growth and proliferation. The activity of mTOR is controlled by amino acids, especially, leucine, one of the branched-chain amino acids, in addition to growth factors and the overall energy supply through the AMP-activated protein kinase. mTOR, in complex with two other proteins, raptor and mLST8, phosphorylates the p70 S6 kinase and the eIF4E binding protein to promote mRNA translation. The signaling pathway upstream of mTOR involves the protein products of the genes mutated in tuberous sclerosis, TSC1 and TSC2, and the small GTPase, Rheb, whose overexpression rescues mTOR from inactivation in vivo by amino acid withdrawal. In this review, we describe recent progress in understanding the control of the mTOR signaling pathway. (C) 2004 Elsevier B.V. All rights reserved.