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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Regulation of the Pro-apoptotic scaffolding protein POSH by Akt

Traci R Lyons1, Jackie Thorburn, Philip W Ryan

  • 1Department of Pathology, the University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.

The Journal of Biological Chemistry
|May 31, 2007
PubMed

Insights

Protein kinase Akt directly phosphorylates POSH, a protein that promotes apoptosis. This phosphorylation reduces POSH

Area of Science:

  • Cellular signaling pathways
  • Apoptosis regulation
  • Protein kinase interactions

Background:

  • Plenty of SH3 domains (POSH) acts as a scaffold, linking Rac to JNK activation and promoting apoptosis.
  • The pro-survival kinase Akt can counteract POSH-induced apoptosis.

Purpose of the Study:

  • To investigate the direct interaction between Akt and POSH.
  • To elucidate the mechanism by which Akt regulates POSH activity and cell survival.

Main Methods:

  • In vivo and in vitro phosphorylation assays.
  • Site-directed mutagenesis to create phosphomimetic mutants (S304D, S304E).
  • Rac binding assays and apoptosis induction studies.

Main Results:

  • Akt directly phosphorylates POSH at serine 304, located in the Rac-binding domain.
  • Phosphorylation and phosphomimetic mutations (S304D/E) decrease POSH's ability to bind activated Rac.
  • The S304D mutant of POSH shows significantly reduced apoptosis-inducing capacity.

Conclusions:

  • Akt-mediated phosphorylation of POSH at serine 304 is a novel mechanism for promoting cell survival.
  • This phosphorylation event inhibits POSH's scaffolding function, thereby reducing Rac-mediated apoptosis.

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