Regulated trafficking and spatially restricted signaling of the epidermal growth factor receptor in human mammary epithelial cells

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Title Regulated trafficking and spatially restricted signaling of the epidermal growth factor receptor in human mammary epithelial cells
Publication Type dissertation
School or College School of Medicine
Department Pathology
Author Burke, Patrick Martin
Date 2000-05
Description The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that regulates the proliferation and physiology of human mammary epithelial cells (HMECs), and dysregulation of receptor activity is associated with mammary epithelial transformation. One mechanism used by HMECs to negatively regulate EGFR signaling is ligand-induced receptor down-regulation. This form of regulated trafficking delivers activated EGFR to the lysosome where they are degraded. This thesis describes additional forms of regulated EGFR trafficking that were discovered in HMECs. In these cells, a significant fraction of the unoccupied EGFR population is located in an intracellular compartment. Rapid, constitutive endocytosis of the unoccupied EGFR creates this distribution. The internalized, unoccupied EGFR are not degraded but are recycled back to the cell surface. Interestingly, the addition of EGF and the activation of a subset of EGFR retards the recycling of the intracellular, unoccupied EGFR. Results presented here also suggest that receptor trafficking performs additional functions. Use of a novel methodology demonstrates that ligand activated EGFR form specific signaling complexes as they transit from the cell surface, through the endosomal compartment and on the way to lysosomes. Together, these findings suggest that the trafficking of the unoccupied EGFR is more complex than we originally suspected, and that the trafficking of occupied EGFR also regulates signal transduction specificity.
Type Text
Publisher University of Utah
Subject Epidermal growth factor; Epithelial cells
Subject MESH Epidermal Growth Factor; Epithelial Cells
Dissertation Institution University of Utah
Dissertation Name PhD
Language eng
Relation is Version of Digital reproduction of "Regulated trafficking and spatially restricted signaling of the epidermal growth factor receptor in human mammary epithelial cells". Spencer S. Eccles Health Sciences Library.
Rights Management © Patrick Martin Burke.
Format application/pdf
Format Medium application/pdf
Format Extent 3,195,555 bytes
Identifier undthes,4240
Source Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available)
Master File Extent 3,195,597 bytes
ARK ark:/87278/s6445pc7
Setname ir_etd
ID 191945
Reference URL https://collections.lib.utah.edu/ark:/87278/s6445pc7
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