It is generally accepted that in endothelial cells the occupation of bradykinin B 2 receptors, which are linked to the guanine nucleotide-dependent regulatory proteins, G i and G q , results in the activation of phospholipase C-β 1 (PLC-β 1 ), followed by a transient increase in the formation of inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol. The PLC-β 1 isoform, in contrast to the γ 1 isoform, is present only at a low level in cultured endothelial cells, implying that PLC-γ 1 activation may play an important role in endothelial signaling pathways. In cultured human endothelial cells, bradykinin induced a rapid increase in the tyrosine phosphorylation of several Triton-soluble proteins. Immunoprecipitation of tyrosine-phosphorylated proteins from bradykinin-stimulated cells followed by Western blotting using the respective antibodies facilitated the identification of a 77 kiloDalton (kDa) protein as paxillin, a 130 kDa protein as PLC-γ 1 , and a 42/44 kDa doublet as mitogen-activated protein (MAP) kinase. The bradykinin-induced tyrosine phosphorylation of PLC-γ 1 was relatively transient and was associated with an increase in intracellular levels of IP 3 . Bradykinin also induced the rapid and transient activation of phosphotyrosine phosphatases localized mainly in the Triton X-100-soluble cell fraction; this tyrosine phosphatase activity was apparently initiated after the release of Ca 2+ from intracellular stores.