Bradykinin activates the Janus-activated kinase/signal transducers and activators of transcription (JAK/STAT) pathway in vascular endothelial cells: Localization of JAK/STAT signalling proteins in plasmalemmal caveolae

Bradykinin (BK) is an important physiological regulator of endothelial cell function. In the present study, we have examined the role of the Janus-activated kinase (JAK)/signal transducers and activators of transcription (STAT) pathway in endothelial signal transduction through the BK B2 receptor (B2R). In cultured bovine aortic endothelial cells (BAECs), BK activates Tyk2 of the JAK family of tyrosine kinases. Activation results in the tyrosine phosphorylation and subsequent nuclear translocation of STAT3. BK also activates the mitogen-activated p44 and p42 protein kinases, resulting in STAT3 serine phosphorylation. Furthermore, Tyk2 and STAT3 form a complex with the B2R in response to BK stimulation. Under basal conditions, Tyk2, STAT3 and the B2R are localized either partially or entirely in endothelial plasmalemmal caveolae. Following BK stimulation of BAECs, however, the B2R and STAT3 are translocated out of caveolae. Taken together, these data suggest that BK activates the JAK/STAT pathway in endothelial cells and that JAK/STAT signalling proteins are localized in endothelial caveolae. Moreover, caveolar localization of the B2R and STAT3 appears to be regulated in an agonist-dependent manner.