The Interplay between Calmodulin and Membrane Interactions with the Pleckstrin Homology Domain of Akt.

ABSTRACT: The Akt protein, a serine/threonine kinase, plays important roles in cell survival, apoptosis, and oncogenes. Akt is translocated to the plasma membrane for activation. Akt-membrane binding is mediated by direct interactions between its pleckstrin homology domain (PHD) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P₃). It has been shown that Akt activation in breast cancer cells is modulated by calmodulin (CaM). However, the molecular mechanism of the interplay between CaM and membrane binding is not established. Here, we employed nuclear magnetic resonance (NMR) and biochemical and biophysical techniques to characterize how PI(3,4,5)P₃, CaM, and membrane mimetics (nanodisc) bind to Akt(PHD). We show that PI(3,4,5)P₃ binding to Akt(PHD) displaces t

SUBMITTER: Agamasu C 

PROVIDER: S-EPMC5217684 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature