title: Phosphorylation of E-cadherin at threonine 790 by protein kinase Cδ reduces β-catenin binding and suppresses the function of E-cadherin.
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, PKCδ 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.
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Chien-Lin
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Wang
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Po-Chao
authors.initials: PC
authors.lastname: Chan
authors.affiliation: Department of Pharmacology, National Cheng Kung University, Tainan 704, Taiwan.|Department of Obstetrics and Gynecology, National Cheng Kung University Hospital, Tainan 704, Taiwan.
authors.forename: Meng-Ru
authors.initials: MR
authors.lastname: Shen
authors.affiliation: Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan.|Graduate Institute of Biomedical Sciences, National Chung Hsing University, Taichung 402, Taiwan.|Rong-Hsing Research Center for Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Hong-Chen
authors.initials: HC
authors.lastname: Chen
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002277:Carcinoma / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology*; D004285:Dogs; D005260:Female; D005455:Fluorescent Antibody Technique; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000378:metabolism* / Q000648:ultrastructure; D061985:Madin Darby Canine Kidney Cells; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D000072417:Protein Domains / Q000502:physiology; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D013912:Threonine / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000473:pathology; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D000199:Actins; D015703:Antigens, CD; C513384:CDH1 protein, human; C495270:CTNNB1 protein, human; D015820:Cadherins; C066855:HGF protein, human; D034741:RNA, Small Interfering; D051176:beta Catenin; D013912:Threonine; D017228:Hepatocyte Growth Factor; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta
keywords: E-cadherin; PKCδ; cell junction; phosphorylation