Cooperative Regulation of Extracellular Signal-Regulated Kinase Activation and Cell Shape Change by Filamin A and β-Arrestins

Autor: Alain Thuret, Olivier Muntaner, Mark G.H. Scott, Vincenzo Pierotti, Julie A. Pitcher, Stephano Marullo, Hélène Storez, Catherine Labbé-Jullié, Erika Lindberg
Přispěvatelé: Laboratory for Molecular Cell Biology and Department of Pharmacology, University College of London [London] (UCL) - MRC, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Wellcome Trust, the Agence Nationale pour la Recherche sur le SIDA, Ligue Contre le Cancer (Comité de l'Oise), CNRS, and INSERM. During the performance of this work, M.G.H.S. was supported by postdoctoral fellowships from the Wellcome Trust, Fondation pou
Rok vydání: 2006
Předmět:
MAPK/ERK pathway
Arrestins
ruffle
Filamin
two hybrid
Contractile Proteins
0302 clinical medicine
Protein Interaction Mapping
beta arrestin
FLNA
Cells
Cultured
beta-Arrestins
Mitogen-Activated Protein Kinase 1
0303 health sciences
Microfilament Proteins
cytoskeleton
Articles
filamin
Cell biology
Repetitive Sequences
Amino Acid
Filamins
Molecular Sequence Data
G protein coupled receptor
Biology
Receptor
Angiotensin
Type 1
03 medical and health sciences
Two-Hybrid System Techniques
Animals
Humans
Immunoprecipitation
Amino Acid Sequence
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
Cell Shape
Molecular Biology
030304 developmental biology
G protein-coupled receptor
Binding Sites
Beta-Arrestins
Cell Membrane
Receptor
Muscarinic M1
Actin cytoskeleton reorganization
Cell Biology
Actin cytoskeleton
MAPK
Angiotensin II
Actins
Protein Structure
Tertiary
Enzyme Activation
Cytoskeletal Proteins
030217 neurology & neurosurgery
Zdroj: Molecular and Cellular Biology
Molecular and Cellular Biology, American Society for Microbiology, 2006, 26, pp.3432-45. 〈10.1128/MCB.26.9.3432-3445.2006〉
ISSN: 1098-5549
0270-7306
Popis: 14 pages; beta-Arrestins (betaarr) are multifunctional adaptor proteins that can act as scaffolds for G protein-coupled receptor activation of mitogen-activated protein kinases (MAPK). Here, we identify the actin-binding and scaffolding protein filamin A (FLNA) as a betaarr-binding partner using Son of sevenless recruitment system screening, a classical yeast two-hybrid system, coimmunoprecipitation analyses, and direct binding in vitro. In FLNA, the betaarr-binding site involves tandem repeat 22 in the carboxyl terminus. betaarr binds FLNA through both its N- and C-terminal domains, indicating the presence of multiple binding sites. We demonstrate that betaarr and FLNA act cooperatively to activate the MAPK extracellular signal-regulated kinase (ERK) downstream of activated muscarinic M1 (M1MR) and angiotensin II type 1a (AT1AR) receptors and provide experimental evidence indicating that this phenomenon is due to the facilitation of betaarr-ERK2 complex formation by FLNA. In Hep2 cells, stimulation of M1MR or AT1AR results in the colocalization of receptor, betaarr, FLNA, and active ERK in membrane ruffles. Reduction of endogenous levels of betaarr or FLNA and a catalytically inactive dominant negative MEK1, which prevents ERK activation, inhibit membrane ruffle formation, indicating the functional requirement for betaarr, FLNA, and active ERK in this process. Our results indicate that betaarr and FLNA cooperate to regulate ERK activation and actin cytoskeleton reorganization.
Databáze: OpenAIRE
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