β-Arrestin2 enhances β2-adrenergic receptor-mediated nuclear translocation of ERK

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.