JNK signaling activity regulates cell-cell adhesions via TM4SF5-mediated p27(Kip1) phosphorylation.
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.
Department of Pharmacy, College of Pharmacy, Cell Dynamics Research Center, Seoul National University, Seoul 151-742, Republic of Korea.
Hyeonjung
H
Kim
Oisun
O
Jung
Minkyung
M
Kang
Mi-Sook
MS
Lee
Doyoung
D
Jeong
Jihye
J
Ryu
Youra
Y
Ko
Yoon-Ju
YJ
Choi
Jung Weon
JW
Lee
D002448:Cell Adhesion; D045744:Cell Line, Tumor; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008565:Membrane Proteins / Q000502:physiology*; D010766:Phosphorylation
C436291:CDKN1B protein, human; D008565:Membrane Proteins; C111029:TM4SF5 protein, human; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048031:JNK Mitogen-Activated Protein Kinases