Involvement of integrin-induced activation of protein kinase C in the formation of adherens junctions

Abstract

In epithelial cells, tight junctions (TJs) and adherens junctions (AJs) form junctional complexes. At AJs, cadherins and nectins are the major cell-cell adhesion molecules. Nectins first form cell-cell adhesions and then recruit cadherins to the nectin-based cell-cell adhesion sites to form AJs in coordination with the activation of integrin αvβ3, followed by the formation of TJs. We previously demonstrated that when MDCK cells precultured at a low Ca2+ concentration were treated with the protein kinase C (PKC) activator 12-O-tetradecanoyl-phorbol-13-acetate (TPA), incomplete AJs and a TJ-like structure were achieved. However, it remains unknown how PKC is activated and how it regulates the formation of cell-cell junctions. When MDCK cells precultured at a low Ca2+ concentration were treated with TPA, incomplete AJs were formed without the activation of integrin αvβ3. Treatment of cells with TPA also enhanced the phosphorylation of FAK, which transmits the outside-in signal of integrin and plays a role in the nectin-induced formation of AJs. In addition, inhibition of PKC suppressed the formation of AJs. These results indicate that the activation of PKC functions downstream of integrin αv β3 and upstream of FAK, and is important for the nectin-induced formation of AJs. © 2007 The Authors Journal compilation © 2007 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.