JNK signaling activity regulates cell–cell adhesions via TM4SF5-mediated p27Kip1 phosphorylation

Transmembrane 4 L six family member 5 (TM4SF5) can regulate cell–cell adhesion and cellular morphology via cytoplasmic p27Kip1-mediated changes in RhoA activity. However, how TM4SF5 causes cytosolic p27Kip1 stabilization remains unknown. In this study we found that TM4SF5-mediated Ser10 phosphorylation of p27Kip1 required for cytosolic localization was not always correlated with Akt activity. Inhibition or suppression of c-Jun N-terminal kinase (JNK) in TM4SF5-expressing cells decreased Ser10 phosphorylation of p27Kip1 and rescued expression levels and localization of adherence junction molecules to cell–cell contacts. These observations suggest involvement of JNKs in TM4SF5-mediated p27Kip1 Ser10 phosphorylation and localization during epithelial–mesenchymal transition.