EGF [Epidermal Growth Factor] internalization and transit the early endosome in HMEC [Human Mammary Epithelial Cells]

Range t1/2 of EGF internalization ~5: transit the early endosome ≥20 min
Organism Human Homo sapiens
Reference Burke P, Schooler K, Wiley HS. Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking. Mol Biol Cell. 2001 Jun12(6):1897-910. p.1906 left column bottom paragraphPubMed ID11408594
Method Abstract: "To directly evaluate EGFR [Epidermal Growth Factor Receptor] signaling during receptor trafficking, [investigators] developed a technique to rapidly and selectively isolate internalized EGFR and associated molecules with the use of reversibly biotinylated anti-EGFR antibodies. In addition, [they] developed antibodies specific to tyrosine-phosphorylated EGFR. With the use of a combination of fluorescence imaging and affinity precipitation approaches, [they] evaluated the state of EGFR activation and substrate association during trafficking in epithelial cells."
Comments P.1906 left column bottom paragraph: "Endocytosis and lysosomal targeting of the EGFR is a normal consequence of receptor activation. Because degradation will inevitably terminate receptor signaling, trafficking of the EGFR has traditionally been viewed in the context of attenuation. Indeed, inhibition of receptor internalization and degradation will enhance signaling. Although EGFR internalization is the first step in receptor degradation, internalization is not necessarily an attenuation process itself. As demonstrated a number of years ago, most EGF associated with cells at steady state is in an intracellular compartment because of the disparity between rates of receptor internalization and rates of lysosomal targeting (Wiley et al., 1985 blue right-pointing triangle). In the case of HMEC, the t1/2 of EGF internalization is ∼5 min, but at least 20 min is required to transit the early endosomes. Thus, at a minimum, there will be at least fourfold more EGF inside the cell than at the surface at steady state. The salient question is whether the internalized ligand-receptor complex is still engaged in productive signaling and whether trafficking processes control signaling specificity."
Entered by Uri M
ID 112722