Regulation of adherens junction protein p120(ctn) by 10 nM CCK precedes actin breakdown in rat pancreatic acini

The initial pathophysiological events that characterize CCK-hyperstimulatio n pancreatitis include the breakdown of the actin filament system and disru ption of cadherin-catenin protein complexes. Cadherins and catenins are par t of adherens junctions, which map act as anchor for the cellular actin fil ament system. We examined the composition and regulation of adherens juncti ons during CCK-induced acinar cell damage. Freshly isolated CCK-stimulated rat pancreatic acini were examined for actin filaments and functional adher ens junctions by immunocytology and laser confocal scanning microscopy or b y coprecipitation and immunoblotting for E-cadherin, beta- and alpha-cateni n, p120(ctn), and phosphotyrosine. In addition to E-cadherin and beta-caten in, acinar cells express the cadherin-regulatory protein p120(ctn) and the attachment protein alpha-catenin. Both colocalize and coimmunoprecipitate w ith E-cadherin in one complex, and all colocalize with the terminal actin w eb. Supramaximal secretory CCK concentrations (10 nM) initiated tyrosine ph osphorylation of p120(ctn) but not of beta-catenin within 2 min, preceding the breakdown of the terminal actin web by several minutes. Under these con ditions, the cadherin-catenin association within the adherens junction; com plex remained intact. We describe for the first time supramaximal CCK-depen dent tyrosine phosphorylation of the adherens junction protein p120(ctn) an d demonstrate the presence:of an intact adherens junction protein complex i n acinar cells. p120(ctn) may participate in the actin filament breakdown d uring experimental conditions mimicking pancreatitis.