A function for Eps15 in EGF-receptor endocytosis?

摘要: Binding of growth factors, such as the epidermal factor (EGF), to their specific receptors on cell surface causes initiation a signal transduction cascade which leads changes in gene expression and finally division. Inactivation EGF-receptor can occur via several mechanisms, receptor transmodulation (Northwood Davis, 1990), dephosphorylation (Faure et al., 1992) down-regulation (for review see Sorkin Waters, 1993). The importance negative regulatory mechanism tyrosine kinase signaling is stressed by observation that defects this regulation facilitate cellular transformation (Wells 1990) tumor formation (Masui 1991). Receptor results loss EGF binding sites from plasma membrane internalization receptors. EGF-receptors enter mediated endocytosis, process involving clathrin coated pits vesicles. coat composed number proteins, adaptor proteins (APs), heavy light chain clathrin, forming lattice Schmid, and, recently has been demonstrated, Eps15 (Tebar 1996; van Delft 1997). Two classes APs have described: AP-1, found trans-Golgi network AP-2, at (Robinson, 1987; Kirchhausen AP-1 heterotetramer two large subunits, γ-adaptin β-adaptin (100–115 kD), medium subunit μl 47 kD small δl 20 kD, whereas AP-2 consists α-adaptin, polypeptides 50 17 (μ2 δ2)(Pearse Robinson, 1984; Keen, 1987). shown bind domain C-terminal tail EGF-receptor, region containing sequence YRAL (Nesterov 1995).