title: Acute activation of β2-adrenergic receptor regulates focal adhesions through βArrestin2- and p115RhoGEF protein-mediated activation of RhoA.
abstract: β(2)-Adrenergic receptors (β(2)ARs) regulate cellular functions through G protein-transduced and βArrestin-transduced signals. β(2)ARs have been shown to regulate cancer cell migration, but the underlying mechanisms are not well understood. Here, we report that β(2)AR regulates formation of focal adhesions, whose dynamic remodeling is critical for directed cell migration. β(2)ARs induce activation of RhoA, which is dependent on βArrestin2 but not G(s). βArrestin2 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 βArrestin2 forms a complex with p115RhoGEF in the cytosol in resting cells. Upon β(2)AR activation, both βArrestin2 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 β(2)ARs in cell migration. These results suggest that βArrestin2 may serve as a convergence point for non-G(12/13) and non-G(q) protein-coupled receptors to activate RhoA.
authors.affiliation: Department of Urology and Prostate Disease Center, University of Florida, Gainesville, Florida 32610, USA.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Ma
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yehia
authors.initials: Y
authors.lastname: Daaka
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Nie
mesh_terms: D051702:Activating Transcription Factor 6; D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D064067:Rho Guanine Nucleotide Exchange Factors; D015398:Signal Transduction / Q000502:physiology*; D000071557:beta-Arrestins; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: C487807:ATF6B protein, human; D051702:Activating Transcription Factor 6; D019390:Arrestins; D050976:Basic-Leucine Zipper Transcription Factors; D020662:Guanine Nucleotide Exchange Factors; D018343:Receptors, Adrenergic, beta-2; D064067:Rho Guanine Nucleotide Exchange Factors; D000071557:beta-Arrestins; C066737:RHOA protein, human; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein