Nitric oxide stimulates tyrosine phosphorylation of p125(FAK) and paxillin in rat pancreatic acini.
Some of the effects of several oncogenes, integrins, growth factors, and neuropeptides are mediated by tyrosine phosphorylation of the non-receptor tyrosine kinase p125(FAK) and the cytoskeletal protein paxillin. We have demonstrated that different stimuli cause tyrosine phosphorylation of p125(FAK) and paxillin in rat pancreatic acini. The aim of the present study was to determine whether exogenous NO activates this pathway. We demonstrate that in isolated rat pancreatic acini, a NO donor, sodium nitroprusside (SNP) stimulates, in a dose- and time-dependent way, tyrosine phosphorylation of p125(FAK) and paxillin. The same effects could be observed after incubating acini with 8-Br-cGMP. Moreover, the stimulation caused by SNP was completely abolished by two different guanylyl cyclase inhibitors, methylene blue, and LY-83583. These inhibitors also diminished unstimulated phosphorylation of p125(FAK) and paxillin. We conclude that in rat pancreatic acini exogenous NO causes p125(FAK) and paxillin tyrosine phosphorylation that is mediated by a guanylyl cyclase-dependent pathway.
Departamento de Fisiología y Farmacología, Universidad de Salamanca, Salamanca, Spain.
M
M
García-Benito
J I
JI
San Román
M A
MA
López
L J
LJ
García-Marín
J J
JJ
Calvo
D000818:Animals; D006152:Cyclic GMP / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D010179:Pancreas / Q000378:metabolism*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014443:Tyrosine
D003598:Cytoskeletal Proteins; D020030:Nitric Oxide Donors; D051419:Paxillin; D010750:Phosphoproteins; C496063:Pxn protein, rat; D009599:Nitroprusside; D009569:Nitric Oxide; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D006152:Cyclic GMP