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Kim, E, Goraksha-Hicks, P, Li, L, Neufeld, TP and Guan, KL (2008) Regulation of TORC1 by Rag GTPases in nutrient response. Nat. Cell Biol. 10:935-45
TORC1 (target of rapamycin complex 1) has a crucial role in the regulation of cell growth and size. A wide range of signals, including amino acids, is known to activate TORC1. Here, we report the identification of Rag GTPases as activators of TORC1 in response to amino acid signals. Knockdown of Rag gene expression suppressed the stimulatory effect of amino acids on TORC1 in Drosophila melanogaster S2 cells. Expression of constitutively active (GTP-bound) Rag in mammalian cells activated TORC1 in the absence of amino acids, whereas expression of dominant-negative Rag blocked the stimulatory effects of amino acids on TORC1. Genetic studies in Drosophila also show that Rag GTPases regulate cell growth, autophagy and animal viability during starvation. Our studies establish a function of Rag GTPases in TORC1 activation in response to amino acid signals.
Amino Acids/pharmacology; Animals; Autophagy; Cell Line; Cell Proliferation; Cell Size; Drosophila Proteins/genetics; Drosophila melanogaster; Food; Humans; Monomeric GTP-Binding Proteins/physiology; Phosphatidylinositol 3-Kinases/genetics; Protein Kinases; RNA, Small Interfering/pharmacology; Signal Transduction