1. MAP1A light chain-2 interacts with GTP-RhoB to control epidermal growth factor (EGF)-dependent EGF receptor signaling
- Author
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Cyril Favard, Daniel Tovar, Barbara Lortal, Isabelle Lajoie-Mazenc, Marie Penary, Anne Pradines, Sophie Allart, Gilles Favre, Meryem Brihoum, Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Institut Claude de Préval (ICP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut FRESNEL (FRESNEL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Claudius Regaud, Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
MESH: Signal Transduction ,MESH: Epidermal Growth Factor ,RHOA ,Receptor expression ,RHOB ,Endocytic cycle ,Fluorescent Antibody Technique ,MESH: Amino Acid Sequence ,MESH: Base Sequence ,Biochemistry ,Epidermal growth factor ,MESH: RNA, Small Interfering ,MESH: Microscopy, Confocal ,RNA, Small Interfering ,rhoB GTP-Binding Protein ,MESH: Fluorescent Antibody Technique ,0303 health sciences ,MESH: Guanosine Triphosphate ,Microscopy, Confocal ,biology ,030302 biochemistry & molecular biology ,Cell biology ,ErbB Receptors ,Endocytic vesicle ,Guanosine Triphosphate ,Microtubule-Associated Proteins ,Protein Binding ,Signal Transduction ,MESH: Cell Line, Tumor ,Endosome ,[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph] ,Molecular Sequence Data ,MESH: Receptor, Epidermal Growth Factor ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,03 medical and health sciences ,Cell Line, Tumor ,MESH: Protein Binding ,Humans ,Amino Acid Sequence ,Molecular Biology ,030304 developmental biology ,MESH: rhoB GTP-Binding Protein ,MESH: Humans ,MESH: Molecular Sequence Data ,Base Sequence ,Epidermal Growth Factor ,Cell Biology ,Actin cytoskeleton ,MESH: Microtubule-Associated Proteins ,biology.protein - Abstract
International audience; Rho GTPases have been implicated in the control of several cellular functions, including regulation of the actin cytoskeleton, cell proliferation, and oncogenesis. Unlike RhoA and RhoC, RhoB localizes in part to endosomes and controls endocytic trafficking. Using a yeast two-hybrid screen and a glutathione S-transferase pulldown assay, we identified LC2, the light chain of the microtubule-associated protein MAP1A, as a novel binding partner for RhoB. GTP binding and the 18-amino acid C-terminal hypervariable domain of RhoB are critical for its binding to MAP1A/LC2. Coimmunoprecipitation and immunofluorescence experiments showed that this interaction occurs in U87 cells. Down-regulation of MAP1A/LC2 expression decreased epidermal growth factor (EGF) receptor expression and modified the signaling response to EGF treatment. We concluded that MAP1A/LC2 is critical for RhoB function in EGF-induced EGF receptor regulation. Because MAP1A/LC2 is thought to function as an adaptor between microtubules and other molecules, we postulate that the RhoB and MAP1A/LC2 interactions facilitate endocytic vesicle trafficking and regulate the trafficking of signaling molecules.
- Published
- 2007