Stimulation of different subtypes of angiotensin II receptors, AT1 and AT2 receptors, regulates STAT activation by negative crosstalk.
Stimulation of different subtypes of angiotensin II receptors, AT1 and AT2 receptors, regulates STAT activation by negative crosstalk.
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DOI：
10.1161/01.res.84.8.876
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发表时间：
1999-04
影响因子：
20.1
通讯作者：
M. Horiuchi;W. Hayashida;M. Akishita;Kouichi Tamura;L. Daviet;J. Lehtonen;V. Dzau
中科院分区：
文献类型：
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作者：
M. Horiuchi;W. Hayashida;M. Akishita;Kouichi Tamura;L. Daviet;J. Lehtonen;V. Dzau
血管紧张素II型2 （AT2）受体对细胞生长具有抑制作用。在本研究中，我们报道了在AT2受体cdna转染的大鼠成年血管平滑肌细胞（VSMCs）中刺激AT2受体抑制血管紧张素II型1 （AT1）受体介导的酪氨酸磷酸化STAT（信号转导和转录激活因子）1 α / β、STAT2和STAT3，而不影响Janus激酶。AT2受体激活还能抑制干扰素、表皮生长因子和血小板源性生长因子诱导的stat1 α / β酪氨酸磷酸化。在表达内源性AT2受体的R3T3成纤维细胞和小鼠胎儿VSMCs中也观察到类似的作用。此外，AT2受体通过抑制细胞外信号调节激酶（ERK）激活来抑制stat1 α和STAT3的丝氨酸磷酸化。刺激AT2受体抑制STATs与c-fos启动子中诱导因子的结合，导致c-fos表达降低。综上所述，我们的研究结果表明AT2受体可以通过抑制ERK和STAT的激活与多个生长受体家族进行负串扰。
Angiotensin II type 2 (AT2) receptor exerts an inhibitory action on cell growth. In the present study, we report that the stimulation of AT2 receptor in AT2 receptor cDNA-transfected rat adult vascular smooth muscle cells (VSMCs) inhibited angiotensin II type 1 (AT1) receptor-mediated tyrosine phosphorylation of STAT (signal transducers and activators of transcription) 1alpha/beta, STAT2, and STAT3 without influence on Janus kinase. AT2 receptor activation also inhibited the tyrosine phosphorylation of STAT1alpha/beta induced by interferon-gamma, epidermal growth factor, and platelet-derived growth factor. Similar effects of AT2 receptor were observed in R3T3 fibroblast and mouse fetal VSMCs, which express endogenous AT2 receptor. Moreover, AT2 receptor inhibited serine phosphorylation of STAT1alpha and STAT3 via the inhibition of extracellular signal-regulated kinase (ERK) activation. Stimulation of AT2 receptor inhibited the binding of STATs with sis-inducing element in c-fos promoter, resulting in decreased c-fos expression. Taken together, our results suggest that AT2 receptor can crosstalk negatively with multiple families of growth receptors by inhibiting ERK and STAT activation.