beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation.
beta-Arrestins were initially shown, in conjunction with G protein-coupled receptor kinases, to be involved in the desensitization and internalization of activated seven-transmembrane receptors. Recently, beta-arrestin 2 has been shown to act as a signal mediator in mitogen-activated protein kinase cascades and to play a positive regulatory role in chemotaxis. We now show that beta-arrestin 1 is required to activate the small GTPase RhoA leading to the re-organization of stress fibers following the activation of the angiotensin II type 1A receptor. This angiotensin II type 1A receptor-directed RhoA activation and stress fiber formation also require the activation of the heterotrimeric G protein G(alphaq/11). Whereas neither beta-arrestin 1 nor G(alphaq/11) activation alone is sufficient to robustly activate RhoA, the concurrent recruitment of beta-arrestin 1 and activation of G(alphaq/11) leads to full activation of RhoA and to the subsequent formation of stress fibers.
Barnes
William G
WG
Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Reiter
Eric
E
Violin
Jonathan D
JD
Ren
Xiu-Rong
XR
Milligan
Graeme
G
Lefkowitz
Robert J
RJ
D000199:Actins / Q000378:metabolism; D019390:Arrestins / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002633:Chemotaxis; D003432:Cross-Linking Reagents / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D004705:Endocytosis; D004789:Enzyme Activation; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D005982:Glutathione Transferase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D007295:Inositol Phosphates / Q000737:chemistry; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
C000605253:ARRB1 protein, human; C000605254:ARRB2 protein, human; D000199:Actins; D019390:Arrestins; D003432:Cross-Linking Reagents; D007295:Inositol Phosphates; D034741:RNA, Small Interfering; D044140:Receptor, Angiotensin, Type 1; D011993:Recombinant Fusion Proteins; D000071559:beta-Arrestin 1; D000071560:beta-Arrestin 2; D000071557:beta-Arrestins; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020742:rhoA GTP-Binding Protein