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  • Title: Recent advances in the regulation of the TOR pathway by insulin and nutrients.
    Author: Avruch J, Lin Y, Long X, Murthy S, Ortiz-Vega S.
    Journal: Curr Opin Clin Nutr Metab Care; 2005 Jan; 8(1):67-72. PubMed ID: 15586002.
    Abstract:
    PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: These findings bring us closer to the understanding of how nutrients and insulin coordinate protein synthesis to regulate anabolic cell growth.
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