PMID:12172554

Citation	Potter, CJ, Pedraza, LG and Xu, T (2002) Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4:658-65
Abstract	The direct mechanism by which the serine/threonine kinase Akt (also known as protein kinase B (PKB)) regulates cell growth is unknown. Here, we report that Drosophila melanogaster Akt/PKB stimulates growth by phosphorylating the tuberous sclerosis complex 2 (Tsc2) tumour suppressor and inhibiting formation of a Tsc1-Tsc2 complex. We show that Akt/PKB directly phosphorylates Drosophila Tsc2 in vitro at the conserved residues, Ser 924 and Thr 1518. Mutation of these sites renders Tsc2 insensitive to Akt/PKB signalling, increasing the stability of the Tsc1-Tsc2 complex within the cell. Stimulating Akt/PKB signalling in vivo markedly increases cell growth/size, disrupts the Tsc1-Tsc2 complex and disturbs the distinct subcellular localization of Tsc1 and Tsc2. Furthermore, all Akt/PKB growth signals are blocked by expression of a Tsc2 mutant lacking Akt phosphorylation sites. Thus, Tsc2 seems to be the critical target of Akt in mediating growth signals for the insulin signalling pathway.
Links	PubMed Online version:10.1038/ncb840
Keywords	Animals; Binding Sites; Cell Division; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/growth & development; Drosophila melanogaster/metabolism; Eye/growth & development; Humans; Insulin/metabolism; Models, Biological; Mutagenesis, Site-Directed; Phosphorylation; Protein-Serine-Threonine Kinases; Proteins/metabolism; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-akt; Repressor Proteins/genetics; Repressor Proteins/metabolism; Signal Transduction; Subcellular Fractions/metabolism; Tumor Suppressor Proteins
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