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Eps15 is recruited to the plasma membrane upon epidermal growth factor receptor activation and localizes to components of the endocytic pathway during receptor internalization

Title: Eps15 is recruited to the plasma membrane upon epidermal growth factor receptor activation and localizes to components of the endocytic pathway during receptor internalization
Authors: M. R. Torrisi; L. V. Lotti; F. Belleudi; R. Gradini; A. E. Salcini; S. Confalonieri; P.G. Pelicci; P.P. Di Fiore
Contributors: M.R. Torrisi; L.V. Lotti; F. Belleudi; R. Gradini; A.E. Salcini; S. Confalonieri; P.G. Pelicci; P.P. Di Fiore
Publication Year: 1999
Collection: The University of Milan: Archivio Istituzionale della Ricerca (AIR)
Subject Terms: Animals; Microtubules; Receptor; Epidermal Growth Factor; Intracellular Signaling Peptides and Proteins; Humans; Tyrosine; Mice; Endosomes; Nerve Tissue Proteins; Adaptor Proteins; Vesicular Transport; Endocytosis; Phosphorylation; Phosphoproteins; Calcium-Binding Proteins; Transfection; Receptors; Platelet-Derived Growth Factor; Cell Membrane; Clathrin; Microscopy; Immunoelectron; Mutation; Cell Line; Settore MED/04 - Patologia Generale
Description: Eps15 is a substrate for the tyrosine kinase of the epidermal growth factor receptor (EGFR) and is characterized by the presence of a novel protein:protein interaction domain, the EH domain. Eps15 also stably binds the clathrin adaptor protein complex AP-2. Previous work demonstrated an essential role for eps15 in receptor-mediated endocytosis. In this study we show that, upon activation of the EGFR kinase, eps15 undergoes dramatic relocalization consisting of 1) initial relocalization to the plasma membrane and 2) subsequent colocalization with the EGFR in various intracellular compartments of the endocytic pathway, with the notable exclusion of coated vesicles. Relocalization of eps15 is independent of its binding to the EGFR or of binding of the receptor to AP-2. Furthermore, eps15 appears to undergo tyrosine phosphorylation both at the plasma membrane and in a nocodazole-sensitive compartment, suggesting sustained phosphorylation in endocytic compartments. Our results are consistent with a model in which eps15 undergoes cycles of association:dissociation with membranes and suggest multiple roles for this protein in the endocytic pathway.
Document Type: article in journal/newspaper
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/9950686; volume:10; issue:2; firstpage:417; lastpage:434; journal:MOLECULAR BIOLOGY OF THE CELL; https://hdl.handle.net/2434/197814; http://www.molbiolcell.org/content/10/2/417
DOI: 10.1091/mbc.10.2.417
Availability: https://hdl.handle.net/2434/197814; https://doi.org/10.1091/mbc.10.2.417; http://www.molbiolcell.org/content/10/2/417
Accession Number: edsbas.5E4C88F1
Database: BASE