BRADYKININ STIMULATES THE TYROSINE PHOSPHORYLATION AND BRADYKININ B2 RECEPTOR ASSOCIATION OF PHOSPHOLIPASE C-GAMMA-1 IN VASCULAR ENDOTHELIAL-CELLS

Bradykinin (BR) B2 receptor signaling involves activation of phospholi pase C (PLC). PLC activation by other receptors consists of either all osteric activation of PLC beta isoforms by G-proteins or tyrosine phos phorylation of PLC gamma isoforms. Because the B2 receptor is a G-prot ein-coupled receptor, it has been assumed that the receptor signals th rough PLC beta. In the present study, however, we have found that BK s timulation 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 pho sphorylation of PLC gamma 1. Phosphorylation is correlated with increa sed LP, production and association of PLC gamma 1 with the C-terminal intracellular domain of the B2 receptor. The B2 receptor can thus phys ically associate with intracellular proteins other than G-proteins. Ac tivation of PLC gamma isoforms, rather than PLC beta isoforms, may, th erefore, be primarily responsible for BK-stimulated IP3 generation in endothelial cells. (C) 1998 Academic Press.