AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration
AT1-receptor heterodimers show enhanced G-protein activation and altered receptor sequestration
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DOI：
10.1038/35024095
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发表时间：
2000-09-07
期刊：
影响因子：
64.8
通讯作者：
Quitterer, U
中科院分区：
文献类型：
--
作者：
AbdAlla, S;Lother, H;Quitterer, U
血管加压素血管紧张素II通过与1型血管紧张素II受体结合调节血管收缩性和血压(AT(1)；参考文献1、2)。缓激肽，一种血管降压药，是血管紧张素II的功能性拮抗剂（参考文献3）。这两种激素系统通过血管紧张素转换酶相互连接，该酶从其前体释放血管紧张素II并使血管抑制剂缓激素失活(4)。在这里，我们发现AT(1)受体和缓激素（B-2）受体也直接相互沟通。它们形成稳定的异源二聚体，导致G α (q)和G α (i)蛋白的激活增加，这是AT触发的两种主要信号蛋白(1)。此外，这两种受体的内吞途径随着异源二聚化而改变。这是由两种不同的血管活性激素受体的异源二聚化引发的信号增强的第一个例子。
The vasopressor angiotensin II regulates vascular contractility and blood pressure through binding to type 1 angiotensin II receptors (AT(1); refs 1, 2). Bradykinin, a vasodepressor, is a functional antagonist of angiotensin II (ref. 3). The two hormone systems are interconnected by the angiotensin-converting enzyme, which releases angiotensin II from its precursor and inactivates the vasodepressor bradykinin(4). Here we show that the AT(1) receptor and the bradykinin (B-2) receptor also communicate directly with each other. They form stable heterodimers, causing increased activation of G alpha(q) and G alpha(i) proteins, the two major signalling proteins triggered by AT(1). Furthermore, the endocytotic pathway of both receptors changed with heterodimerization. This is the first example of signal enhancement triggered by heterodimerization of two different vasoactive hormone receptors.