Endothelin A and Endothelin B Receptors Differ in Their Ability to Stimulate ERK1/2 Activation
Endothelin A and Endothelin B Receptors Differ in Their Ability to Stimulate ERK1/2 Activation
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内皮素 A 和内皮素 B 受体刺激 ERK1/2 激活的能力不同
DOI：
10.3181/00379727-231-2310757
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发表时间：
2006
影响因子：
3.2
通讯作者：
A. Oksche
中科院分区：
文献类型：
--
作者：
E. Grantcharova;H. Reusch;M. Beyermann;W. Rosenthal;A. Oksche
内皮素-1（ET-1）作用于两种不同的G蛋白偶联受体，即内皮素A（ETA）和内皮素B（ET B）受体。两种受体亚型在其组织表达和信号转导方面均显示出差异。在本研究中，我们比较了ETA和ETB受体刺激细胞外信号调节激酶1/2（ERK 1/2）的能力。此外，我们分析了ERK 1/2激活的细胞外N端的作用，因为ETB受体经历激动剂依赖性N端蛋白水解。ET-1刺激稳定表达ETA受体的HEK 293细胞可诱导单相但持续的ERK 1/2激活，而ETB受体则显示出双相的ERK 1/2激活。缺失蛋白水解切割的N末端的截短突变型ETB受体（Δ2-64 ETB）仅显示出双相和瞬时ERK 1/2激活。用ET-1和合成的NT 27 -64肽（对应于ETB受体和ET-1的N-末端切割片段）处理HEK 293 Δ2-64 ETB细胞克隆，不能恢复ERK 1/2的双相激活。其中N末端被ETA受体的N末端替换的嵌合ETB受体引起双相ERK 1/2活化。所提出的数据表明，一个完整的N末端的ETB受体是必要的ERK 1/2激活的第二阶段。然而，看来N末端的长度而不是特定的序列基序是双相ERK 1/2激活所必需的。
Endothelin-1 (ET-1) acts on two different G protein–coupled receptors, namely the endothelin A (ETA) and the endothelin B (ETB) receptors. Both receptor subtypes show differences in their tissue expression and signal transduction. In the present study, we compared the ability of ETA and ETB receptors to stimulate extracellular signal-regulated kinase 1/2 (ERK1/2). In addition, we analyzed the role of the extracellular N terminus for ERK1/2 activation, because the ETB receptor undergoes an agonist-dependent N-terminal proteolysis. ET-1 stimulation of HEK293 cells stably expressing the ETA receptor induced a monophasic, but sustained ERK1/2 activation, whereas the ETB receptor showed a biphasic ERK1/2 activation. A truncated mutant ETB receptor, lacking the proteolytically cleaved N terminus (Δ2-64 ETB) revealed only a monophasic and transient ERK1/2 activation. Treatment of HEK293 Δ2-64 ETB cell clones with ET-1 and a synthetic NT27-64 peptide, corresponding to the N-terminally cleaved fragment of the ETB receptor and ET-1, did not restore the biphasic activation of ERK1/2. A chimeric ETB receptor in which the N terminus was replaced by the N terminus of the ETA receptor elicited biphasic ERK1/2 activation. The presented data suggest that an intact N terminus of the ETB receptor is necessary for the second phase of ERK1/2 activation. However, it appears that the length of the N terminus rather than a specific sequence motif is required for biphasic ERK1/2 activation.
影响因子：
64.8
作者：
YANAGISAWA, M;KURIHARA, H;MASAKI, T
通讯作者：
MASAKI, T