Effect of bradykinin on tyrosine kinase and phosphatase activities and cell proliferation in mesangial cells

We investigated the relationship between protein tyrosine phosphorylation a nd bradykinin (BK) receptor activation in rat mesangial cells (MC). Stimula tion of the B2 receptor resulted in a dual effect consisting of an independ ent activation and inhibition of tyrosine kinase activity (TKA). The activa tion was rapid and transient, reaching a peak value at 30 s whereas the inh ibition was observed at 5 min and persisted up to 10 min. Treatments with p ertussis-toxin and U73122 showed that only the BK-induced stimulation of TK A is dependent on phospholipase C activation via a, pertussis-toxin sensiti ve G-protein. In addition, BK induced an increase in tyrosine phosphatase a ctivity. Western-blot analysis demonstrated that the dual effect of BK on T KA was associated with both an increase and a decrease in tyrosine phosphor ylation of the p125-focal adhesion kinase (FAK). Moreover, BK was able to r educe the maximal stimulated MC cell proliferation induced by fetal calf se rum. These data show that in rat MC, B2 receptor stimulation activates and inhibits two independent tyrosine kinase signaling pathways associated with tyrosine phosphorylation of p125-FAK that might be implicated in MC prolif eration. (C) 1999 Elsevier Science B.V. All rights reserved.