Acute Activation of beta(2)-Adrenergic Receptor Regulates Focal Adhesions through beta Arrestin2-and p115RhoGEF Protein-mediated Activation of RhoA

作者：Ma Xiaojie; Zhao Yu; Daaka Yehia; Nie Zhongzhen^*

来源：Journal of Biological Chemistry, 2012, 287(23): 18925-18936.

DOI：10.1074/jbc.M112.352260

beta(2)-Adrenergic receptors (beta(2)ARs) regulate cellular functions through G protein-transduced and beta Arrestin-transduced signals. beta(2)ARs have been shown to regulate cancer cell migration, but the underlying mechanisms are not well understood. Here, we report that beta(2)AR regulates formation of focal adhesions, whose dynamic remodeling is critical for directed cell migration. beta(2)ARs induce activation of RhoA, which is dependent on beta Arrestin2 but not G(s). beta Arrestin2 forms a complex with p115RhoGEF, a guanine nucleotide exchange factor for RhoA that is well known to be activated by G(12/13)-coupled receptors. Our results show that beta Arrestin2 forms a complex with p115RhoGEF in the cytosol in resting cells. Upon beta(2)AR activation, both beta Arrestin2 and p115RhoGEF translocate to the plasma membrane, with concomitant activation of RhoA and formation of focal adhesions and stress fibers. Activation of RhoA and focal adhesion remodeling may explain, at least in part, the role of beta(2)ARs in cell migration. These results suggest that beta Arrestin2 may serve as a convergence point for non-G(12/13) and non-G(q) protein-coupled receptors to activate RhoA.

• 出版日期2012-6-1