Nitric oxide stimulates tyrosine phosphorylation of p125(FAK) and paxillinin rat pancreatic acini

Some of the effects of several oncogenes, integrins, growth factors, and ne uropeptides are mediated by tyrosine phosphorylation of the non-receptor ty rosine kinase p125(FAK) and the cytoskeletal protein paxillin. We have demo nstrated 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) st imulates, in a dose- and time-dependent way, tyrosine phosphorylation of p1 25(FAK) and paxillin. The same effects could be observed after incubating a cini with 8-Br-cGMP. Moreover, the stimulation caused by SNP was completely abolished by two different guanylyl cyclase inhibitors, methylene blue, an d LY-83583, These inhibitors also diminished unstimulated phosphorylation o f p125(FAK) and paxillin. We conclude that in rat pancreatic acini exogenou s NO causes p125(FAK) and paxillin tyrosine phosphorylation that is mediate d by a guanylyl cyclase-dependent pathway. (C) zooo Academic Press.