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Potter, C.J., Pedraza, L.G., Xu, T. (2002). Akt regulates growth by directly phosphorylating Tsc2.  Nat. Cell Biol. 4(9): 658--665.
FlyBase ID
FBrf0152244
Publication Type
Research paper
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.

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Review

TSC<down>1</down>-TSC<down>2</down>: a complex tale of PKB-mediated S6K regulation.
McManus and Alessi, 2002, Nat. Cell Biol. 4(9): E214--E216 [FBrf0161485]

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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Nat. Cell Biol.
    Title
    Nature Cell Biology
    Publication Year
    1999-
    ISBN/ISSN
    1465-7392 1476-4679
    Data From Reference