Akt regulates growth by directly phosphorylating Tsc2

Christopher J Potter, Laura G. Pedraza, Tian Xu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)658-665
Number of pages8
JournalNature Cell Biology
Volume4
Issue number9
DOIs
StatePublished - Sep 2002
Externally publishedYes

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Tuberous Sclerosis
Proto-Oncogene Proteins c-akt
Growth
Cell Enlargement
Drosophila Proteins
Tuberous Sclerosis 2
Protein-Serine-Threonine Kinases
Drosophila
Phosphorylation
Insulin
Mutation

ASJC Scopus subject areas

  • Cell Biology

Cite this

Akt regulates growth by directly phosphorylating Tsc2. / Potter, Christopher J; Pedraza, Laura G.; Xu, Tian.

In: Nature Cell Biology, Vol. 4, No. 9, 09.2002, p. 658-665.

Research output: Contribution to journalArticle

Potter, Christopher J ; Pedraza, Laura G. ; Xu, Tian. / Akt regulates growth by directly phosphorylating Tsc2. In: Nature Cell Biology. 2002 ; Vol. 4, No. 9. pp. 658-665.
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