Involvement of integrin-induced activation of protein kinase C in the formation of adherens junctions.
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 alpha(v)beta(3), followed by the formation of TJs. We previously demonstrated that when MDCK cells precultured at a low Ca(2+) 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 Ca(2+) concentration were treated with TPA, incomplete AJs were formed without the activation of integrin alpha(v)beta(3). 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 alpha(v)beta(3) and upstream of FAK, and is important for the nectin-induced formation of AJs.
Ozaki
Misa
M
The Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita, Osaka 565-0871, Japan.
Ogita
Hisakazu
H
Takai
Yoshimi
Y
D022005:Adherens Junctions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D000081247:CSK Tyrosine-Protein Kinase; D002118:Calcium / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004285:Dogs; D004789:Enzyme Activation; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008954:Models, Biological; D000075983:Nectins; D011493:Protein Kinase C / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D019061:src-Family Kinases
D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; D000075983:Nectins; D011994:Recombinant Proteins; C113183:FAK-related nonkinase; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium