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PMID:15611106

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Citation

Barnes, WG, Reiter, E, Violin, JD, Ren, XR, Milligan, G and Lefkowitz, RJ (2005) beta-Arrestin 1 and Galphaq/11 coordinately activate RhoA and stress fiber formation following receptor stimulation. J. Biol. Chem. 280:8041-50

Abstract

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.

Links

PubMed Online version:10.1074/jbc.M412924200

Keywords

Actins/metabolism; Arrestins/metabolism; Arrestins/physiology; Cell Line; Chemotaxis; Cross-Linking Reagents/pharmacology; Cytoskeleton/metabolism; Dimerization; Electrophoresis, Polyacrylamide Gel; Endocytosis; Enzyme Activation; GTP-Binding Protein alpha Subunits, Gq-G11/physiology; Glutathione Transferase/metabolism; Green Fluorescent Proteins/metabolism; Humans; Immunoblotting; Immunoprecipitation; Inositol Phosphates/chemistry; Mitogen-Activated Protein Kinase 1/metabolism; Mitogen-Activated Protein Kinase 3/metabolism; Models, Biological; Protein Binding; RNA Interference; RNA, Small Interfering/metabolism; Receptor, Angiotensin, Type 1/metabolism; Recombinant Fusion Proteins/metabolism; Signal Transduction; Time Factors; Transfection; rhoA GTP-Binding Protein/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:AGTR1

enables

GO:0001596: angiotensin type I receptor activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:AGTR1

involved_in

GO:0007266: Rho protein signal transduction

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:AGTR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P32121

F

Seeded From UniProt

complete

HUMAN:AGTR1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P49407

F

Seeded From UniProt

complete

HUMAN:ARRB2

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB2

located_in

GO:0031410: cytoplasmic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB1

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB1

located_in

GO:0031410: cytoplasmic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB1

enables

GO:0005096: GTPase activator activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:ARRB1

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB1

part_of

GO:0031410: cytoplasmic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB1

enables

GO:0031701: angiotensin receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P30556

F

Seeded From UniProt

complete

HUMAN:ARRB1

involved_in

GO:0035025: positive regulation of Rho protein signal transduction

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ARRB1

involved_in

GO:0043149: stress fiber assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ARRB2

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB2

part_of

GO:0031410: cytoplasmic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:ARRB2

enables

GO:0031701: angiotensin receptor binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P30556

F

Seeded From UniProt

complete

HUMAN:GNAQ

enables

GO:0005096: GTPase activator activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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