Akt phosphorylates both Tsc1 and Tsc2 in Drosophila, but neither phosphorylation is required for normal animal growth.
Akt, an essential component of the insulin pathway, is a potent inducer of tissue growth. One of Akt's phosphorylation targets is Tsc2, an inhibitor of the anabolic kinase TOR. This could account for part of Akt's growth promoting activity. Although phosphorylation of Tsc2 by Akt does occur in vivo, and under certain circumstances can lead to reduced Tsc2 activity, the functional significance of this event is unclear since flies lacking Akt phosphorylation sites on Tsc2 are viable and normal in size and growth rate. Since Drosophila Tsc1, the obligate partner of Tsc2, has an Akt phosphorylation motif that is not conserved in mammals, we investigate here whether Akt redundantly phosphorylates the Tsc complex on Tsc1 and Tsc2. We provide evidence that Akt phosphorylates Tsc1 at Ser533. We show that flies lacking Akt phosphorylation sites on Tsc1 alone, or on both Tsc1 and Tsc2 concurrently, are viable and normal in size. This shows that phosphorylation of the Tsc1/2 complex by Akt is not required for Akt to activate TORC1 and to promote tissue growth in Drosophila.
Schleich
Sibylle
S
German Cancer Research Center (DKFZ), Heidelberg, Germany.
Teleman
Aurelio A
AA
D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism*; D017931:DNA Primers; D004330:Drosophila / Q000254:growth & development*; D029721:Drosophila Proteins / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D018797:Cell Cycle Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; C515347:TSC1 protein, Drosophila; C117726:gig protein, Drosophila; D051057:Proto-Oncogene Proteins c-akt