| Publication Type |
dissertation |
| School or College |
School of Medicine |
| Department |
Pathology |
| Author |
Dong, Jianying |
| Title |
Regulation of ligand release and receptor signaling by the membrane-anchoring domains of epidermal growth factor receptor ligands |
| Date |
2000-05 |
| Description |
The epidermal growth factor receptor (EGFR) plays an important role in transducing extracellular signals into a variety of biological responses. Ligand binding initiates receptor signaling. To date, six ligands have been identified for the EGF receptor: EGF, TGF alpha, amphiregulin, HB-EGF, betacellulin, and epiregulin. All are initially synthesized as membrane-anchored precursor proteins and subsequently released through regulated proteolysis. This dissertation investigates the role of the membrane-anchoring domain of EGFR ligands in regulating ligand release and receptor signaling. Ligand release was found to be required for efficient activation of EGFR by some ligands, such as EGF and TGF alpha, suggesting that the membrane-anchoring domain spatially restricts ligand availability and receptor activation. Using a domain-swapping strategy, two engineered ligands were made with the membrane-anchoring domains of EGF and HB-EGF respectively. These two ligands showed distinct patterns of trafficking and secretion resembling those of EGF and HB-EGF. This indicates that the membrane-anchoring domains of EGFR ligands dictate their localization and release. In addition, the ligand anchored via the HB-EGF membrane-anchoring domain was able to activate EGFR without being released. Thus, the membrane-anchoring domains of EGFR ligands also modulate their ability to signal as soluble or membrane-bound forms. The conclusions from these studies suggest that different EGFR ligands may perform different |
| Type |
Text |
| Publisher |
University of Utah |
| Subject |
Metalloprotease |
| Subject MESH |
Ligands; Receptors, Cell Surface; Epidermal Growth Factor |
| Dissertation Institution |
University of Utah |
| Dissertation Name |
PhD |
| Language |
eng |
| Relation is Version of |
Digital reproduction of "Regulation of ligand release and receptor signaling by the membrane-anchoring domains of epidermal growth factor receptor ligands." Spencer S. Eccles Health Sciences Library. Print version of "Regulation of ligand release and receptor signaling by the membrane-anchoring domains of epidermal growth factor receptor ligands." available at J. Willard Marriott Library Special Collection, QH9.7 2000 .D65 |
| Rights Management |
© Jianying Dong. |
| Format Medium |
application/pdf |
| Format Extent |
2,910,795 bytes |
| Identifier |
undthes,4850 |
| Source |
Original: University of Utah Spencer S. Eccles Health Sciences Library (no longer available). |
| Master File Extent |
2,910,853 bytes |
| ARK |
ark:/87278/s6qf8vpv |
| Setname |
ir_etd |
| ID |
191058 |
| Reference URL |
https://collections.lib.utah.edu/ark:/87278/s6qf8vpv |
