A role for phosphoinositides in tyrosine phosphorylation of p125 focal adhesion kinase in rat pancreatic acini

Previous studies have shown that different agonists increase tyrosine phosp horylation of the focal adhesion related proteins p125(FAK), p130(Cas), and paxillin in different cell types and that tyrosine phosphorylation depends on the integrity of the actin cytoskeleton. Because phosphoinositides are important for the maintenance of the cytoskeleton, the role of phosphoinosi tides in the tyrosine phosphorylation of these proteins in response to occu pancy of m3 muscarinic and CCKA receptors has been investigated in pancreat ic acini. Addition of carbachol or CCK-8 to pancreatic acini resulted in ra pid increases in the tyrosine phosphorylation of p125(FAK), p130(Cas), and paxillin. Pretreatment of pancreatic acini with LY294002 or wortmannin resu lted in a concentration-dependent inhibition of tyrosine phosphorylation of p125(FAK), p130(Cas), and paxillin stimulated by carbachol or CCK-8. Carba chol- or CCK-8-stimulated tyrosine phosphorylation of these proteins was no t inhibited by rapamycin, PD 98059 or SE 203580, and thus it was dissociate d from the activation of p70 S6 or MAP kinases. These results indicate that m3 muscarinic and CCKA receptor-mediated increase in p125(FAK) , p130(Cas) , and paxillin tyrosine phosphorylation in pancreatic acini depends on the ability of these cells to synthesise phosphoinositides. (C) 2000 Elsevier S cience inc. All rights reserved.