Reference Report

Reference
Citation	Potter, C.J., Pedraza, L.G., Xu, T. (2002). Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4(9): 658--665. (Export to RIS)
FlyBase ID	FBrf0152244
Publication Type	Research paper
PubMed ID	12172554
PubMed 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.
DOI
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
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
Alleles (19)
	Akt1^{hs.T:Uuuu\Myr4} Akt1^{Scer\UAS.T:Ivir\HA1} gig^{MtnA.T:Zzzz\FLAG} gig^{MtnA.ΔAkt-P.T:Zzzz\FLAG} gig^{S924A.Scer\UAS.T:Zzzz\FLAG} gig^{S924A.T1518A.Scer\UAS.T:Zzzz\FLAG} gig^{Scer\UAS.T:Zzzz\FLAG} gig^{T437A.T1054A.Scer\UAS.T:Zzzz\FLAG} gig^{T1518A.Scer\UAS.T:Zzzz\FLAG} gig^{ΔAkt-P.Scer\UAS.T:Zzzz\FLAG} Hsap\RPS6KB1^D4.Scer\UAS S6k^Scer\UAS.cWa Scer\GAL4^Act5C.PI Scer\GAL4^ey.PH Scer\GAL4^GMR.PF Scer\GAL4^{Scer\FRT.Act5C} Tsc1^{MtnA.T:Hsap\MYC} Tsc1^Q600X Tsc1^{Scer\UAS.T:Hsap\MYC}
Constructs (14)
	P{Act5C-GAL4} P{AyGAL4} P{GAL4-ey.H} P{GAL4-ninaE.GMR} P{UAS-Akt1.HA} P{UAS-gig.FLAG} P{UAS-gig.S924A.FLAG} P{UAS-gig.S924A.T1518A.FLAG} P{UAS-gig.T437A.T1054A.FLAG} P{UAS-gig.T1518A.FLAG} P{UAS-gig.ΔAkt-P.FLAG} P{UAS-p70S6K1.D4} P{UAS-S6k.W} P{UAS-Tsc1.MYC}
Genes (10)
	Akt1 gig Hsap\RPS6KB1 S6k Scer\GAL4 T:Hsap\MYC T:Ivir\HA1 T:Uuuu\Myr4 T:Zzzz\FLAG Tsc1