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 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
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DOI：
10.1042/0264-6021:3510257
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发表时间：
2000-10-01
影响因子：
4.1
通讯作者：
Venema, RC
中科院分区：
文献类型：
--
作者：
Ju, H;Venema, VJ;Venema, RC
缓激肽（BK）是内皮细胞功能的重要生理调节因子。在本研究中，我们研究了Janus激活的激酶（JAK）/信号转导和转录激活因子（STAT）途径在内皮细胞信号转导中的作用，通过BK B2受体（B2 R）。在培养的牛主动脉内皮细胞（BAEC）中，BK激活酪氨酸激酶JAK家族的Tyk 2。活化导致STAT 3的酪氨酸磷酸化和随后的核转位。BK还激活促分裂原激活的p44和p42蛋白激酶，导致STAT 3丝氨酸磷酸化。此外，Tyk 2和STAT 3响应于BK刺激而与B2 R形成复合物。在基础条件下，Tyk 2，STAT 3和B2 R定位于部分或全部在内皮细胞质膜小窝。然而，在BK刺激BAEC后，B2 R和STAT 3易位出小窝。总之，这些数据表明，BK激活JAK/STAT通路在内皮细胞和JAK/STAT信号蛋白定位在内皮细胞小窝。此外，B2 R和STAT 3的小窝定位似乎以激动剂依赖性方式调节。
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 JAR/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.