JNK phosphorylates beta-catenin and regulates adherens junctions.
The c-Jun amino-terminal kinase (JNK) is an important player in inflammation, proliferation, and apoptosis. More recently, JNK was found to regulate cell migration by phosphorylating paxillin. Here, we report a novel role of JNK in cell adhesion. Specifically, we provide evidence that JNK binds to E-cadherin/beta-catenin complex and phosphorylates beta-catenin at serine 37 and threonine 41, the sites also phosphorylated by GSK-3beta. Inhibition of JNK kinase activity using dominant-negative constructs reduces phosphorylation of beta-catenin and promotes localization of E-cadherin/beta-catenin complex to cell-cell contact sites. Conversely, activation of JNK induces beta-catenin phosphorylation and disruption of cell contacts, which are prevented by JNK siRNA. We propose that JNK binds to beta-catenin and regulates formation of adherens junctions, ultimately controlling cell-to-cell adhesion.
Lee
Meng-Horng
MH
Bioengineering Laboratory, 908 Furnas Hall, Department of Chemical and Biological Engineering, University at Buffalo, State University of New York, Amherst, NY 14260, USA.
Koria
Piyush
P
Qu
Jun
J
Andreadis
Stelios T
ST
D022005:Adherens Junctions / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D007231:Infant, Newborn; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
D015820:Cadherins; D051176:beta Catenin; D012694:Serine; D048031:JNK Mitogen-Activated Protein Kinases