TY - JOUR
T1 - Epidermal growth factor pathway substrate 15, Eps15
AU - Salcini, Anna Elisabetta
AU - Chen, Hong
AU - Iannolo, Gioacchin
AU - De Camilli, Pietro
AU - Di Fiore, Pier Paolo
PY - 1999/8
Y1 - 1999/8
N2 - Eps15 was originally identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR). Eps15 has a tripartite structure comprising a NH2-terminal portion, which contains three EH domains, a central putative coiled-coil region, and a COOH-terminal domain containing multiple copies of the amino acid triplet Aspartate-Proline-Phenylalanine. A pool of Eps15 is localized at clathrin coated pits where it interacts with the clathrin assembly complex AP-2 and a novel AP-2 binding protein, Epsin. Perturbation of Eps15 and Epsin function inhibits receptor-mediated endocytosis of EGF and transferrin, demonstrating that both proteins are components of the endocytic machinery. Since the family of EH-containing proteins is implicated in various aspects of intracellular sorting, biomolecular strategies aimed at interfering with these processes can now be envisioned. These strategies have potentially far reaching implications extending to the control of cell proliferation. In this regard, it is of note that Eps15 has the potential of transforming NIH-3T3 cells and that the eps15 gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias, thus implicating this protein in the subversion of cell proliferation in neoplasia. Copyright (C) 1999 Elsevier Science Ltd.
AB - Eps15 was originally identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR). Eps15 has a tripartite structure comprising a NH2-terminal portion, which contains three EH domains, a central putative coiled-coil region, and a COOH-terminal domain containing multiple copies of the amino acid triplet Aspartate-Proline-Phenylalanine. A pool of Eps15 is localized at clathrin coated pits where it interacts with the clathrin assembly complex AP-2 and a novel AP-2 binding protein, Epsin. Perturbation of Eps15 and Epsin function inhibits receptor-mediated endocytosis of EGF and transferrin, demonstrating that both proteins are components of the endocytic machinery. Since the family of EH-containing proteins is implicated in various aspects of intracellular sorting, biomolecular strategies aimed at interfering with these processes can now be envisioned. These strategies have potentially far reaching implications extending to the control of cell proliferation. In this regard, it is of note that Eps15 has the potential of transforming NIH-3T3 cells and that the eps15 gene is rearranged with the HRX/ALL/MLL gene in acute myelogeneous leukemias, thus implicating this protein in the subversion of cell proliferation in neoplasia. Copyright (C) 1999 Elsevier Science Ltd.
KW - Endocytosis
KW - Eps15
KW - Epsin
KW - Transport
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U2 - 10.1016/S1357-2725(99)00042-4
DO - 10.1016/S1357-2725(99)00042-4
M3 - Article
C2 - 10481267
AN - SCOPUS:0032865109
VL - 31
SP - 805
EP - 809
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
SN - 1357-2725
IS - 8
ER -