14‐3‐3:PRAS40 interaction mediates an Akt proliferative signal

Abstract

Multiple growth factors induce PRAS40 phosphorylation at threonine 246. This residue appears to be primarily phosphorylated by Akt, however, evidence also exists for Akt-independent phosphorylation. Serine to alanine mutation demonstrates the requirement of this residue for 14-3-3 binding. Expression of an active Akt construct in cos-7 cells results in the increased activity of a reporter gene in a viability assay, suggesting an increase in proliferation. Co-expression of wild type PRAS40 has little effect on the Akt mediated proliferation increase, while a threonine 246 to alanine PRAS40 mutant attenuates the increase. These results suggest a role for PRAS40:14-3-3 association in the modulation of Akt signaling.