β-Arrestin2 enhances β2-adrenergic receptor-mediated nuclear translocation of ERK
β-Arrestin2 enhances β2-adrenergic receptor-mediated nuclear translocation of ERK
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DOI：
10.1016/j.cellsig.2004.12.014
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发表时间：
2005-10-01
影响因子：
4.8
通讯作者：
Kurose, H
中科院分区：
文献类型：
--
作者：
Kobayashi, H;Narita, Y;Kurose, H
β-Arrestin介导β-肾上腺素能受体（β AR）的脱敏和内化，但也在细胞外信号调节激酶（ERK）级联中充当支架蛋白。因此，我们研究了β-arrestin 2在β AR介导的ERK信号通路中的作用。异丙肾上腺素刺激在表达β（1）AR或β（2）AR的COS-7细胞中同样激活细胞质和细胞核ERK。然而，在表达β 2 AR的细胞中，β-arrestin 2的共表达增强了细胞核ERK的活性，而在表达β 1 AR的细胞中则没有。百日咳毒素治疗和G β-γ作用的阻断抑制了β-arrestin 2增强的ERK核活化，表明β-arrestin 2在受体刺激后以G β-γ依赖性机制促进ERK核定位。含有β（1）AR羧基末端区域的β（2）AR失去了β-arrestin 2促进的核转位。由于羧基末端区域对于β-arrestin结合是重要的，这些结果表明，β-arrestin 2募集到β（2）AR的羧基末端区域对于ERK定位到细胞核是重要的。(c)2005年爱思唯尔公司All rights reserved.
beta-Arrestin mediates desensitization and internalization of beta-adrenergic receptors (beta ARs), but also acts as a scaffold protein in extracellular signal-regulated kinase (ERK) cascade. Thus, we have examined the role of beta-arrestin2 in the beta AR-mediated ERK signaling pathways. Isoproterenol stimulation equally activated cytoplasmic and nuclear ERK in COS-7 cells expressing beta(1)AR or beta(2)AR. However, the activity of nuclear ERK was enhanced by co-expression of beta-arrestin2 in beta(2)AR-but not beta(1)AR-expressing cells. Pertussis toxin treatment and blockade of G beta gamma action inhibited beta-arrestin2-enhanced nuclear activation of ERK, suggesting that beta-arrestin2 promotes nuclear ERK localization in a G beta gamma dependent mechanism upon receptor stimulation. beta(2)AR containing the carboxyl terminal region of beta(1)AR lost the beta-arrestin2-promoted nuclear translocation. As the carboxyl terminal region is important for beta-arrestin binding, these results demonstrate that recruitment of beta-arrestin2 to carboxyl terminal region of beta(2)AR is important for ERK localization to the nucleus. (c) 2005 Elsevier Inc. All rights reserved.