Cholecystokinin-induced redistribution of paxillin in rat pancreatic acinar cells

Cholecystokinin (CCK) dose-dependently stimulates enzyme secretion or loss of cell integrity in the exocrine pancreas. Signaling mechanims include tyr osine phosphorylation of p125(FAK) and paxillin. Here, we examine their pot ential function. Maximum phosphorylation of both proteins was observed afte r stimulation of freshly isolated rat pancreatic acini with 10 nM CCK, a co ncentration known to initiate breakdown of the terminal actin web and cell damage. Under these conditions, CCK initiated transient redistribution of p axillin from the apical cytosol to the apical and lateral plasmamembrane wi thin 2 min, where it colocalized with the terminal actin web. Relocation of paxillin was confirmed in subcellular fractions by western blotting and co incided with maximum phosphorylation of membrane-bound p125FAK and paxillin . Subsequently, paxillin was redistributed to the basolateral cytosol and w as degraded. p125(FAK) remained membrane-bound. We conclude that phosphoryl ation and redistribution of paxillin and phosphorylation of p125FAK may par ticipate in the CCK-induced disassembly of acinar cell actin. (C) 1999 Acad emic Press.