Acidic extracellular pH induces p120-catenin-mediated disruption of adherens junctions via the Src kinase-PKCδ pathway.
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.
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Ying
Y
Chen
Hsiu-Ni
HN
Kung
Chia-Hui
CH
Chen
Shih-Horng
SH
Huang
Kuo-Hsin
KH
Chen
Seu-Mei
SM
Wang
D022005:Adherens Junctions / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D051177:Catenins / Q000378:metabolism*; D004791:Enzyme Inhibitors; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051571:Protein Kinase C-alpha / Q000235:genetics / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D034741:RNA, Small Interfering; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000095002:Delta Catenin
D051177:Catenins; D004791:Enzyme Inhibitors; D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D012694:Serine; D019061:src-Family Kinases; C496628:PRKCA protein, human; C497258:PRKCD protein, human; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D000095002:Delta Catenin; C000722347:CTNND1 protein, human