Acidic extracellular pH induces p120-catenin-mediated disruption of adherens junctions via the Src kinase-PKCδ pathway

Ying Chen; Hsiu-Ni Kung; Chia-Hui Chen; Shih-Horng Huang; Kuo-Hsin Chen; Seu-Mei Wang

doi:10.1016/j.febslet.2011.01.022

Acidic extracellular pH induces p120-catenin-mediated disruption of adherens junctions via the Src kinase-PKCδ pathway

FEBS Lett. 2011 Feb 18;585(4):705-10. doi: 10.1016/j.febslet.2011.01.022. Epub 2011 Jan 18.

Authors

Ying Chen¹, Hsiu-Ni Kung, Chia-Hui Chen, Shih-Horng Huang, Kuo-Hsin Chen, Seu-Mei Wang

Affiliation

¹ Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.

PMID: 21251911
DOI: 10.1016/j.febslet.2011.01.022

Abstract

An acidic microenvironment induces disruption of adherens junctions (AJs) of hepatoma cells. This study investigated the impact of an acidic extracellular pH (pHe) on p120-catenin (p120-ctn) serine phosphorylation. pH 6.6 treatment increased intracellular calcium levels, activated protein kinase C (PKC)α and PKCδ, and decreased serine phosphorylation of p120-ctn. Further knockdown of PKCα and δ by small interference RNA (siRNA) prevented the pH 6.6-induced downregulation of p120-ctn at AJ and the serine dephosphorylation of p120-ctn. Moreover, PP2 pretreatment and siRNA of c-Src abrogated the pH 6.6-induced PKCδ activation. Together, the c-Src-PKCδ cascade and PKCα regulate the acidic pHe-induced AJ disruption.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adherens Junctions / metabolism*
Calcium Signaling / drug effects
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Catenins / metabolism*
Delta Catenin
Enzyme Inhibitors
Hep G2 Cells
Humans
Hydrogen-Ion Concentration
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Phosphorylation
Protein Kinase C-alpha / genetics
Protein Kinase C-alpha / metabolism
Protein Kinase C-delta / antagonists & inhibitors
Protein Kinase C-delta / genetics
Protein Kinase C-delta / metabolism*
Protein Kinase Inhibitors / pharmacology
Protein Processing, Post-Translational
RNA Interference
RNA, Small Interfering
Serine / metabolism
Signal Transduction*
Time Factors
src-Family Kinases / antagonists & inhibitors
src-Family Kinases / genetics
src-Family Kinases / metabolism*

Substances

Catenins
Enzyme Inhibitors
Protein Kinase Inhibitors
RNA, Small Interfering
Serine
src-Family Kinases
PRKCA protein, human
PRKCD protein, human
Protein Kinase C-alpha
Protein Kinase C-delta
Delta Catenin
CTNND1 protein, human