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 phosphorylation 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 phosphoinositides in the tyrosine phosphorylation of these proteins in response to occupancy of m3 muscarinic and CCK(A) receptors has been investigated in pancreatic acini. Addition of carbachol or CCK-8 to pancreatic acini resulted in rapid increases in the tyrosine phosphorylation of p125(FAK), p130(Cas), and paxillin. Pretreatment of pancreatic acini with LY294002 or wortmannin resulted in a concentration-dependent inhibition of tyrosine phosphorylation of p125(FAK), p130(Cas), and paxillin stimulated by carbachol or CCK-8. Carbachol- or CCK-8-stimulated tyrosine phosphorylation of these proteins was not inhibited by rapamycin, PD 98059 or SB 203580, and thus it was dissociated from the activation of p70 S6 or MAP kinases. These results indicate that m3 muscarinic and CCK(A) 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.
Rosado
J A
JA
Department of Physiology, University of Extremadura, 10080-, Cáceres, Spain. jarosado@unex.es
Salido
G M
GM
García
L J
LJ
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D051419:Paxillin; D010716:Phosphatidylinositols / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011506:Proteins; D051381:Rats; D017208:Rats, Wistar; D050717:Retinoblastoma-Like Protein p130; D012844:Sincalide / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism*
C493843:Bcar1 protein, rat; D015815:Cell Adhesion Molecules; D050719:Crk-Associated Substrate Protein; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D051419:Paxillin; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D011506:Proteins; C496063:Pxn protein, rat; D050717:Retinoblastoma-Like Protein p130; D014443:Tyrosine; D002217:Carbachol; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D012844:Sincalide; D002118:Calcium