p120ctn binds to the membrane-proximal region of the E-cadherin cytoplasmic domain and is involved in modulation of adhesion activity

被引:148
作者
Ohkubo, T [1 ]
Ozawa, M [1 ]
机构
[1] Kagoshima Univ, Fac Med, Dept Biochem, Kagoshima 8908520, Japan
关键词
D O I
10.1074/jbc.274.30.21409
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cadherins are transmembrane glycoproteins involved in Ca2+-dependent cell-cell adhesion. Previously, we showed that the conserved membrane-proximal region of the E cadherin cytoplasmic domain negatively regulates adhesion activity. In this report, we provide several lines of evidence that p120(ctn) is involved in this negative regulation. p120(ctn) binds to the membrane-proximal region of the nonfunctional carboxyl-terminally deleted E-cadherin protein. An additional internal deletion in this region prevented the association with p120(ctn) and activated the protein, as seen in an aggregation assay. Furthermore, the nonfunctional E-cadherin can be activated through coexpression of p120(ctn) proteins with amino-terminal deletions, which eliminate several potential serine/threonine phosphorylation sites but do not affect the ability to bind to cadherins, Finally, we show that staurosporine, a kinase inhibitor, induces an increased electrophoretic mobility of p120(ctn) bound to E-cadherin polypeptides, activates the nonfunctional E-cadherin protein, and converts the wildtype E-cadherin and an E-cadherin-alpha-catenin chimeric protein from a cytochalasin D-sensitive to a cytochalasin D-insensitive state. Together, these results indicate that p120(ctn) is a modulator of E-cadherin-mediated cell adhesion.
引用
收藏
页码:21409 / 21415
页数:7
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