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The Journal of Biological Chemistry 283, 7 (2008) 4155-64
MAP1A light chain-2 interacts with GTP-RhoB to control epidermal growth factor (EGF)-dependent EGF receptor signaling.
Isabelle Lajoie-Mazenc 1, Daniel Tovar, Marie Penary 2, Barbara Lortal, Sophie Allart, Cyril Favard 3, 4, Meryem Brihoum, Anne Pradines 2, Gilles Favre 2
(2008-02-15)

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.
1:  Centre de Physiopathologie Toulouse Purpan
INSERM : U563 – IFR30 – Université Paul Sabatier [UPS] - Toulouse III – IFR150
2:  Departement /u563 : Oncogenèse, Signalisation et Innovation thérapeutique
INSERM : U563 – Université Paul Sabatier [UPS] - Toulouse III – Institut Claudius Regaud
3:  Institut FRESNEL (IF)
CNRS : UMR6133 – Université de Provence - Aix-Marseille I – Université Paul Cézanne - Aix-Marseille III – Ecole Centrale de Marseille
4:  Institut de pharmacologie et de biologie structurale (IPBS)
CNRS : UMR5089 – Université Paul Sabatier [UPS] - Toulouse III
Physics/Physics/Biological Physics

Life Sciences/Cellular Biology