NDLI: Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis and Intracellular Trafficking

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Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis and Intracellular Trafficking

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Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis and Intracellular Trafficking

Content Provider	PubMed Central
Author	Burke, Patrick Schooler, Kevin Wiley, H. Steven
Editor	Brugge, Joan S.
Copyright Year	2001
Abstract	Ligand activation of the epidermal growth factor receptor (EGFR) leads to its rapid internalization and eventual delivery to lysosomes. This process is thought to be a mechanism to attenuate signaling, but signals could potentially be generated after endocytosis. To directly evaluate EGFR signaling during receptor trafficking, we developed a technique to rapidly and selectively isolate internalized EGFR and associated molecules with the use of reversibly biotinylated anti-EGFR antibodies. In addition, we developed antibodies specific to tyrosine-phosphorylated EGFR. With the use of a combination of fluorescence imaging and affinity precipitation approaches, we evaluated the state of EGFR activation and substrate association during trafficking in epithelial cells. We found that after internalization, EGFR remained active in the early endosomes. However, receptors were inactivated before degradation, apparently due to ligand removal from endosomes. Adapter molecules, such as Shc, were associated with EGFR both at the cell surface and within endosomes. Some molecules, such as Grb2, were primarily found associated with surface EGFR, whereas others, such as Eps8, were found only with intracellular receptors. During the inactivation phase, c-Cbl became EGFR associated, consistent with its postulated role in receptor attenuation. We conclude that the association of the EGFR with different proteins is compartment specific. In addition, ligand loss is the proximal cause of EGFR inactivation. Thus, regulated trafficking could potentially influence the pattern as well as the duration of signal transduction.
Starting Page	1897
File Format	PDF
ISSN	10591524
Journal	Molecular Biology of the Cell
Issue Number	6
Volume Number	12
Language	English
Publisher	The American Society for Cell Biology
Publisher Date	2001-06-01
Access Restriction	Open
Rights Holder	The American Society for Cell Biology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology

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Endosomal Accumulation of the Activated Epidermal Growth Factor Receptor (EGFR) Induces Apoptosis

Calmodulin Regulates Intracellular Trafficking of Epidermal Growth Factor Receptor and the MAPK Signaling Pathway

Spatial Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis

Ligand-activated epidermal growth factor receptor (EGFR) signaling governs endocytic trafficking of unliganded receptor monomers by non-canonical phosphorylation

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Protein-tyrosine Phosphatase 1B Modulates Early Endosome Fusion and Trafficking of Met and Epidermal Growth Factor Receptors

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Regulation of Epidermal Growth Factor Receptor Signaling by Endocytosis and Intracellular Trafficking

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