Phosphorylation of E-cadherin at threonine 790 by protein kinase C? reduces ?-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)?, 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, PKC? is phosphorylated and activated by Src, which then phosphorylates E-cadherin at Thr790. Phosphorylation of E-cadherin at Thr790 diminishes its interaction with ?-catenin and impairs the homophilic interaction between the ectodomains of E-cadherin. The suppression of PKC? by its dominant-negative mutants or specific short-hairpin RNA inhibits the disruption of cell-cell adhesions induced by hepatocyte growth factor. Elevated PKC? expression in cancer cells is correlated with increased phosphorylation of E-cadherin at Thr790, reduced binding of E-cadherin to ?-catenin, and poor homophilic interaction between E-cadherin. Analysis of surgical specimens confirmed that PKC? is overexpressed in cervical cancer tissues, accompanied by increased phosphorylation of E-cadherin at Thr790. Together, our findings unveil a negative role for PKC? in cell-cell adhesion through phosphorylation of E-cadherin.

SUBMITTER: Chen CL 

PROVIDER: S-EPMC5095074 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature