Regulation of the Pro-apoptotic scaffolding protein POSH by Akt.

POSH (Plenty of SH3 domains) binds to activated Rac and promotes apoptosis by acting as a scaffold to assemble a signal transduction pathway leading from Rac to JNK activation. Overexpression of POSH induces apoptosis in a variety of cell types, but apoptosis can be prevented by co-expressing the pro-survival protein ...
kinase Akt. We report here that POSH is a direct substrate for phosphorylation by Akt in vivo and in vitro, and we identify a major site of Akt phosphorylation as serine 304 of POSH, which lies within the Rac-binding domain. We further show that phosphorylation of POSH results in a decreased ability to bind activated Rac, as does phosphomimetic S304D and S304E mutation of POSH. S304D mutant POSH also shows a strongly reduced ability to induce apoptosis. These findings identify a novel mechanism by which Akt promotes cell survival.
Mesh Terms:
Apoptosis, Base Sequence, Cell Line, Cloning, Molecular, Humans, Kidney, Molecular Sequence Data, Proto-Oncogene Proteins c-akt, Recombinant Fusion Proteins, Restriction Mapping, Reverse Transcriptase Polymerase Chain Reaction, Ubiquitin-Protein Ligases
J. Biol. Chem.
Date: Jul. 27, 2007
Download Curated Data For This Publication
127739
Switch View:
  • Interactions 2