Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin

Chien Lin Chen, Shu Hui Wang, Po Chao Chan, Meng-Ru Shen, Hong Chen Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Proper control of cell-cell adhesion is crucial for embryogenesis and tissue homeostasis. In this study, we show that protein kinase C (PKC)δ, a member of the novel PKC subfamily, localizes at cell-cell contacts of epithelial cells through its C2-like domain in an F-actin-dependent manner. Upon hepatocyte growth factor stimulation, PKCd is phosphorylated and activated by Src, which then phosphorylates E-cadherin at Thr790. Phosphorylation of E-cadherin at Thr790 diminishes its interaction with β-catenin and impairs the homophilic interaction between the ectodomains of E-cadherin. The suppression of PKCδ by its dominant-negative mutants or specific short-hairpin RNA inhibits the disruption of cell-cell adhesions induced by hepatocyte growth factor. Elevated PKCδ expression in cancer cells is correlated with increased phosphorylation of E-cadherin at Thr790, reduced binding of E-cadherin to β-catenin, and poor homophilic interaction between E-cadherin. Analysis of surgical specimens confirmed that PKCδ is overexpressed in cervical cancer tissues, accompanied by increased phosphorylation of E-cadherin at Thr790. Together, our findings unveil a negative role for PKCδ in cell-cell adhesion through phosphorylation of E-cadherin.

Original languageEnglish
Pages (from-to)37260-37276
Number of pages17
JournalOncotarget
Volume7
Issue number24
DOIs
Publication statusPublished - 2016 Jan 1

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Catenins
Threonine
Cadherins
Protein Kinase C
Phosphorylation
Cell Adhesion
Hepatocyte Growth Factor
Uterine Cervical Neoplasms
Small Interfering RNA
Embryonic Development
Actins
Homeostasis
Epithelial Cells

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Chen, Chien Lin ; Wang, Shu Hui ; Chan, Po Chao ; Shen, Meng-Ru ; Chen, Hong Chen. / Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin. In: Oncotarget. 2016 ; Vol. 7, No. 24. pp. 37260-37276.
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Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin. / Chen, Chien Lin; Wang, Shu Hui; Chan, Po Chao; Shen, Meng-Ru; Chen, Hong Chen.

In: Oncotarget, Vol. 7, No. 24, 01.01.2016, p. 37260-37276.

Research output: Contribution to journalArticle

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