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-hyperstimulation pancreatitis include the breakdown of the actin filament system and disruption of cadherin-catenin protein complexes. Cadherins and catenins are part of adherens junctions, which may act as anchor for the cellular actin filament system. We examined the composition and regulation of adherens junctions during CCK-induced acinar cell damage. Freshly isolated CCK-stimulated rat pancreatic acini were examined for actin filaments and functional adherens junctions by immunocytology and laser confocal scanning microscopy or by coprecipitation and immunoblotting for E-cadherin, beta- and alpha-catenin, p120(ctn), and phosphotyrosine. In addition to E-cadherin and beta-catenin, acinar cells express the cadherin-regulatory protein p120(ctn) and the attachment protein alpha-catenin. Both colocalize and coimmunoprecipitate with E-cadherin in one complex, and all colocalize with the terminal actin web. Supramaximal secretory CCK concentrations (10 nM) initiated tyrosine phosphorylation of p120(ctn) but not of beta-catenin within 2 min, preceding the breakdown of the terminal actin web by several minutes. Under these conditions, the cadherin-catenin association within the adherens junction complex remained intact. We describe for the first time supramaximal CCK-dependent tyrosine phosphorylation of the adherens junction protein p120(ctn) and demonstrate the presence of an intact adherens junction protein complex in acinar cells. p120(ctn) may participate in the actin filament breakdown during experimental conditions mimicking pancreatitis.
Leser
J
J
Department of Internal Medicine I, University of Ulm, 89070 Ulm, Germany.
Beil
M F
MF
Musa
O A
OA
Adler
G
G
Lutz
M P
MP
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002766:Cholecystokinin / Q000494:pharmacology / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D010179:Pancreas / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D015534:Trans-Activators; D014443:Tyrosine / Q000378:metabolism; D051176:beta Catenin; D000095002:Delta Catenin
D000199:Actins; D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D015534:Trans-Activators; D051176:beta Catenin; D014443:Tyrosine; D002766:Cholecystokinin; D000095002:Delta Catenin; C000722355:Ctnnd1 protein, rat