JNK signaling activity regulates cell-cell adhesions via TM4SF5-mediated p27(Kip1) phosphorylation

Cancer Lett. 2012 Jan 28;314(2):198-205. doi: 10.1016/j.canlet.2011.09.030. Epub 2011 Oct 19.

Abstract

Transmembrane 4L six family member 5 (TM4SF5) can regulate cell-cell adhesion and cellular morphology via cytoplasmic p27(Kip1)-mediated changes in RhoA activity. However, how TM4SF5 causes cytosolic p27(Kip1) stabilization remains unknown. In this study we found that TM4SF5-mediated Ser10 phosphorylation of p27(Kip1) 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 p27(Kip1) and rescued expression levels and localization of adherence junction molecules to cell-cell contacts. These observations suggest involvement of JNKs in TM4SF5-mediated p27(Kip1) Ser10 phosphorylation and localization during epithelial-mesenchymal transition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Epithelial-Mesenchymal Transition
  • Humans
  • JNK Mitogen-Activated Protein Kinases / physiology*
  • MAP Kinase Signaling System*
  • Membrane Proteins / physiology*
  • Phosphorylation

Substances

  • CDKN1B protein, human
  • Membrane Proteins
  • TM4SF5 protein, human
  • Cyclin-Dependent Kinase Inhibitor p27
  • JNK Mitogen-Activated Protein Kinases