Regulation of β2‑adrenergic receptor cell surface expression by interaction with cystic fibrosis transmembrane conductance regulator‑associated ligand (CAL)
Regulation of β2‑adrenergic receptor cell surface expression by interaction with cystic fibrosis transmembrane conductance regulator‑associated ligand (CAL)
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通过与囊性纤维化跨膜电导调节器相关配体 (CAL) 相互作用调节β2-肾上腺素能受体细胞表面表达
DOI：
10.1007/s00726-015-1965-6
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发表时间：
2015
期刊：
影响因子：
3.5
通讯作者：
He Junqi
中科院分区：
文献类型：
--
作者：
Yang Longyan;Zheng Junfang;Xiong Ying;Meng Ran;Ma Qian;Liu Hua;Shen Hui;Zheng Shuai;Wang Songlin;He Junqi
β 2肾上腺素能受体（β2AR）是GPCR的成员，可激活多种信号通路，是心力衰竭的重要治疗靶点。然而，β 2 AR信号调节的分子机制尚不完全清楚。在这项研究中，我们发现囊性纤维化跨膜传导调节相关配体（CAL）过表达减少β 2 AR介导的细胞外信号调节激酶1/2（ERK 1/2）激活。进一步的研究表明CAL是β 2 AR的一种新的结合伴侣。CAL主要通过受体的第三胞内环（ICL 3）和CAL的卷曲螺旋结构域与β 2 AR结合，这与β 1 AR的羧基端（CT）和CAL的PDZ结构域介导的CAL/β 1 AR相互作用不同，CAL过表达抑制了高尔基体中β 2 AR的表达，并降低了质膜中β 2 AR的表达。
The beta-2 adrenergic receptor (β2AR), a member of GPCR, can activate multiple signaling pathways and is an important treatment target for cardiac failure. However, the molecular mechanism about β2AR signaling regulation is not fully understood. In this study, we found that cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) overexpression reduced β2AR-mediated extracellular signal-regulated kinase-1/2 (ERK1/2) activation. Further study identified CAL as a novel binding partner of β2AR. CAL is associated with β2AR mainly via the third intracellular loop (ICL3) of receptor and the coiled-coil domains of CAL, which is distinct from CAL/β1AR interaction mediated by the carboxyl terminal (CT) of β1AR and PDZ domain of CAL. CAL overexpression retarded β2AR expression in Golgi apparatus and reduced the receptor expression in plasma membrane.