Linkage between G protein-coupled receptors and the Jak/STAT pathway in cardiovascular cells

Janus激活的激酶/信号转换器和转录路径的激活者（Jak/STAT路径）是一种用于细胞因子的稳定信号转换系统。This pathway is activated following stimulation of the type I angiotensin II （AT-D21-D2） receptor in vas？smooth muscle cells。为了测试这一途径是在其他G蛋白偶受体之间共享的，我们研究了α-D21和D2肾上腺素受体之间的联系。在人类umbilical artery smooth muscle cells中发现的Tyrosine phosphorylation of Jak 2，Tyk 2， and STAT 1。Jak 2的磷酸化是由α-D21-D2受体拮抗剂前列腺素和α-D21 B-D2-特定的氯乙基胆碱能预防的，但不是α-D21 A-D2-特定的WB 4101，而STAT 1的磷酸化是由前列腺素和Jak 2-特定的酪氨酸激酶抑制剂AG 490抑制的。After stimulation with phenylephrine， Jak2 and STAT 1 were found to associate with Oracle D21B Oracle D2 receptor。Phenylephrine刺激了STAT 1的DNA绑定活动。However， phenylephrine并没有承诺它的状态3。最近，Jak/STAT路径曾建议在由Interleukin 6-相关细胞因子诱导的心脏病myocyte hypertrophy的发展中扮演一个关键角色。因此，我们对这个路径中的媒介vascular smooth muscle hypertrophy induced by al-D21-D2 agonists很感兴趣。由phenyllephrine促进的蛋白质合成是由Prazosin，AG 490抑制的，并对STAT 1的decoy寡核苷酸的介绍。这是一个愚蠢的主意，第三阶段是无效的。These results suggested that D21 agonist stimulates STAT 1 through activation of Jak2 and Tyk2 and that this pathway mediates D21 agonist-induced smooth muscle hypertrophy。

The Janus-activated kinase/signal transducers and activators of transcription pathway (Jak/STAT pathway) is an established signal transduction system for cytokines. This pathway is activated following stimulation of the type I angiotensin II (ATィイD21ィエD2) receptor in vascular smooth muscle cells. To examine whether this pathway is shared among other G-protein-coupled receptors, we studied the linkage between the αィイD21ィエD2 adrenergic receptor and this pathway. The αィイD21ィエD2 agonist phenylephrine (100nM) induced tyrosine phosphorylation of Jak2, Tyk2, and STAT1 in human umbilical artery smooth muscle cells. The phosphorylation of Jak2 was prevented by the αィイD21ィエD2 receptor antagonists prazosin and αィイD21BィエD2-specific chloroethylcolonidine, but not by αィイD21AィエD2-specific WB4101, and the phosphorylation of STAT1 was inhibited by prazosin and Jak2-specific tyrosine kinase inhibitor AG490. After stimulation with phenylephrine, Jak2 and STAT1 were found to associate with αィイD21BィエD2 receptor. Phenylephrine stimulated the DNA binding activity of STAT1. However, phenylephrine did not promote that of STAT3. Recently the Jak/STAT pathway has been suggested to play a key role in the development of cardiac myocyte hypertrophy induced by interleukin 6-related cytokines. Therefore we were interested in whether this pathway mediates vascular smooth muscle hypertrophy induced by αィイD21ィエD2 agonists. Protein synthesis promoted by phenylephrine was inhibited by prazosin, AG490, and the introduction of a decoy oligonucleotide for STAT1. However a decoy for STAT3 was ineffective. These results suggested that αィイD21ィエD2 agonist stimulates STAT1 through activation of Jak2 and Tyk2 and that this pathway mediates αィイD21ィエD2 agonist-induced smooth muscle hypertrophy.