Differential kinetic and spatial patterns of β-arrestin and G protein-mediated ERK activation by the angiotensin II receptor
Differential kinetic and spatial patterns of β-arrestin and G protein-mediated ERK activation by the angiotensin II receptor
复制标题
DOI：
10.1074/jbc.m405878200
复制
发表时间：
2004-08-20
影响因子：
4.8
通讯作者：
Lefkowitz, RJ
中科院分区：
文献类型：
--
作者：
Ahn, SK;Shenoy, SK;Lefkowitz, RJ
七跨膜血管紧张素II 1A型受体通过依赖于G蛋白(可能是G（q)/G(11)）或β -阻滞蛋白2的不同途径激活丝裂原活化蛋白激酶细胞外信号调节激酶1和2 （ERK1/2）。在这里，我们试图区分这两种机制激活的ERK1/2的动力学和空间模式。我们利用β -抑制素RNA干扰、蛋白激酶C抑制剂Ro-31-8425、突变型血管紧张素II受体（DRY/AAY）和突变型血管紧张素II肽（SII-angiotensin），在HEK-293细胞中分离出这两种途径，它们不能激活G蛋白。G蛋白依赖性激活快速（峰值）
The seven-membrane-spanning angiotensin II type 1A receptor activates the mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 (ERK1/2) by distinct pathways dependent on either G protein (likely G(q)/G(11)) or beta-arrestin2. Here we sought to distinguish the kinetic and spatial patterns that characterize ERK1/2 activated by these two mechanisms. We utilized beta-arrestin RNA interference, the protein kinase C inhibitor Ro-31-8425, a mutant angiotensin II receptor (DRY/AAY), and a mutant angiotensin II peptide (SII-angiotensin), which are incapable of activating G proteins, to isolate the two pathways in HEK-293 cells. G protein-dependent activation was rapid (peak