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

TY - JOUR

T1 - Eps15 is recruited to the plasma membrane upon epidermal growth factor receptor activation and localizes to components of the endocytic pathway during receptor internalization.

AU - Torrisi, M R

AU - Lotti, L V

AU - Belleudi, F

AU - Gradini, R

AU - Salcini, A E

AU - Confalonieri, S

AU - Pelicci, P G

AU - Di Fiore, P P

N1 - Keywords: Adaptor Proteins, Vesicular Transport; Animals; Calcium-Binding Proteins; Cell Line; Cell Membrane; Clathrin; Endocytosis; Endosomes; Humans; Intracellular Signaling Peptides and Proteins; Mice; Microscopy, Immunoelectron; Microtubules; Mutation; Nerve Tissue Proteins; Phosphoproteins; Phosphorylation; Receptor, Epidermal Growth Factor; Receptors, Platelet-Derived Growth Factor; Transfection; Tyrosine

PY - 1999

Y1 - 1999

N2 - 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.

AB - 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.

M3 - Journal article

C2 - 9950686

SN - 1059-1524

VL - 10

SP - 417

EP - 434

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

IS - 2

ER -