Effect of bradykinin on tyrosine kinase and phosphatase activities and cell proliferation in mesangial cells.
We investigated the relationship between protein tyrosine phosphorylation and bradykinin (BK) receptor activation in rat mesangial cells (MC). Stimulation of the B2 receptor resulted in a dual effect consisting of an independent activation and inhibition of tyrosine kinase activity (TKA). The activation was rapid and transient, reaching a peak value at 30 s whereas the inhibition was observed at 5 min and persisted up to 10 min. Treatments with pertussis-toxin and U73122 showed that only the BK-induced stimulation of TKA is dependent on phospholipase C activation via a pertussis-toxin sensitive G-protein. In addition, BK induced an increase in tyrosine phosphatase activity. Western-blot analysis demonstrated that the dual effect of BK on TKA was associated with both an increase and a decrease in tyrosine phosphorylation of the p125-focal adhesion kinase (FAK). Moreover, BK was able to reduce the maximal stimulated MC cell proliferation induced by fetal calf serum. 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 proliferation.
Alric
C
C
Institut National de la Sante et de la Recherche Médicale U388, Institut Louis Bugnard, C.H.U. Rangueil, Toulouse, France.
Pecher
C
C
Bascands
J L
JL
Girolami
J P
JP
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D004963:Estrenes / Q000494:pharmacology; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D005920:Glomerular Mesangium / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D006131:Growth Inhibitors / Q000494:pharmacology; D037342:Pertussis Toxin; D010766:Phosphorylation / Q000187:drug effects; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015815:Cell Adhesion Molecules; D004963:Estrenes; D006131:Growth Inhibitors; D011760:Pyrrolidinones; D010566:Virulence Factors, Bordetella; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D014443:Tyrosine; D037342:Pertussis Toxin; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D017027:Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D001920:Bradykinin