Regulation of β2-adrenergic receptor cell surface expression by interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL)
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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.
KeywordsAdrenergic receptor PDZ homology Coiled-coil domain CAL Intracellular loop
Cystic fibrosis transmembrane conductance regulator-associated ligand
Extracellular signal-regulated kinase
This work was supported by the National Natural Science Foundation of the People’s Republic of China (No. 81272887 and 81372739), Beijing Municipal Natural Science Foundation (No. 7131003), the Foundation of Beijing Educational Committee (No. KM201110025002), the Importation and Development of High-Caliber Talents Project of Beijing Municipal Institutions (CIT&TCD201304187). The manuscript revision by Dr. Qiong Qin was highly appreciated.
Conflict of interest
We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work; there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.
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