Functional molecular imaging of ILK-mediated Akt/PKB signaling cascades and the associated role of β-parvin

Visualization and quantification of the dynamics of protein-protein interactions in living cells can be used to explore the macromolecular events involved in signal transduction processes. In this study, functional molecular imaging using a luciferase-based complementation method demonstrated how the integrin-linked kinase (ILK)-mediated protein complex controls downstream signals. The luciferase complementation assay showed that Akt1 preferentially binds to β-parvin rather than to ILK within the complex. Moreover, photon flux from the interaction between β-parvin and Akt1 increased following serum stimulation, and the β-parvin-Akt1 interaction was dependent on phosphoinositide 3-kinase. Intriguingly, small interfering (si)RNA-mediated β-parvin knockdown increased photon flux from the interaction between ILK and Akt1, leading to stabilization of hypoxia-inducible factor-1α and increased expression of vascular endothelial growth factor-A. These data from functional molecular imaging demonstrated that β-parvin plays a regulatory role in the ILK-mediated Akt (also called protein kinase B) signaling cascades, suggesting that β-parvin might be a crucial modulator of cell survival.