Bradykinin stimulates the tyrosine phosphorylation and bradykinin B2 receptor association of phospholipase C gamma 1 in vascular endothelial cells.
Bradykinin (BK) B2 receptor signaling involves activation of phospholipase C (PLC). PLC activation by other receptors consists of either allosteric activation of PLC beta isoforms by G-proteins or tyrosine phosphorylation of PLC gamma isoforms. Because the B2 receptor is a G-protein-coupled receptor, it has been assumed that the receptor signals through PLC beta. In the present study, however, we have found that BK stimulation of IP3 production and the Ca2+ signal in endothelial cells is dependent on tyrosine phosphorylation. Furthermore, stimulation of B2 receptors in these cells is accompanied by a transient tyrosine phosphorylation of PLC gamma 1. Phosphorylation is correlated with increased IP3 production and association of PLC gamma 1 with the C-terminal intracellular domain of the B2 receptor. The B2 receptor can thus physically associate with intracellular proteins other than G-proteins. Activation of PLC gamma isoforms, rather than PLC beta isoforms, may, therefore, be primarily responsible for BK-stimulated IP3 generation in endothelial cells.
Venema
V J
VJ
Department of Pediatrics, Medical College of Georgia, Augusta 30912, USA. rvenema@mail.mcg.edu
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Sun
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Eaton
D C
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Marrero
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MB
Venema
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RC
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism*; D004789:Enzyme Activation; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis; D007527:Isoenzymes / Q000378:metabolism*; D051966:Phospholipase C gamma; D010766:Phosphorylation; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin / Q000378:metabolism; D018002:Receptors, Bradykinin / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D007527:Isoenzymes; D011720:Pyrazoles; D011743:Pyrimidines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D043782:Receptor, Bradykinin B2; D011945:Receptors, Angiotensin; D018002:Receptors, Bradykinin; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D015544:Inositol 1,4,5-Trisphosphate; D019061:src-Family Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D001920:Bradykinin