title: Recent advances in the regulation of the TOR pathway by insulin and nutrients.
abstract: OBJECTIVE
  The aim of this article is to summarize recent advances in the understanding of the regulation of the target of rapamycin (TOR), a protein kinase that is regulated independently by insulin, amino acids and energy sufficiency and which participates in the control of the component of protein synthesis responsible for cell growth.
  
  
  RESULTS
  These have been found in two major areas: genetic studies in Drosophila followed by studies in mammalian systems have identified the components of the Tuberous Sclerosis protein complex, a heterodimer of the proteins Hamartin and Tuberin, as inhibitors of TOR signaling, and as the major targets by which the insulin/IGF-1 signal transduction pathway, through the protein kinase PKB, and the energy status of the cell, through the AMP-activated protein kinase, regulate the TOR signaling. In turn, the inhibitory action of the tuberous sclerosis protein complex has been shown to be mediated by its ability to deactivate the small, ras-like GTPase Rheb. A second advance has been achieved by the identification of the TOR-associated protein raptor, as an indispensable substrate binding sub-unit of the TOR complex, and as the site at which the inhibitory effects on TOR signaling of rapamycin and amino acid deficiency converge.
  
  
  CONCLUSIONS
  These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth.
authors.affiliation: Diabetes Unit and Medical Services and Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA. avruch@molbio.harvard.edu
authors.forename: Joseph
authors.initials: J
authors.lastname: Avruch
authors.forename: Yenshou
authors.initials: Y
authors.lastname: Lin
authors.forename: Xiaomeng
authors.initials: X
authors.lastname: Long
authors.forename: Sid
authors.initials: S
authors.lastname: Murthy
authors.forename: Sara
authors.initials: S
authors.lastname: Ortiz-Vega
mesh_terms: D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D020690:GTPase-Activating Proteins; D007328:Insulin; D009479:Neuropeptides; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins