Akt regulates growth by directly phosphorylating Tsc2
- PMID: 12172554
- DOI: 10.1038/ncb840
Akt regulates growth by directly phosphorylating Tsc2
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.
Comment in
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TSC1-TSC2: a complex tale of PKB-mediated S6K regulation.Nat Cell Biol. 2002 Sep;4(9):E214-6. doi: 10.1038/ncb0902-e214. Nat Cell Biol. 2002. PMID: 12205484 No abstract available.
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High intensity anticoagulation for cardioversion of atrial arrhythmias? The shocking truth.J Am Coll Cardiol. 2002 Sep 4;40(5):934-6. doi: 10.1016/s0735-1097(02)02064-8. J Am Coll Cardiol. 2002. PMID: 12225718 No abstract available.
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