Role of the interaction of proHB-EGF with heparan sulfate proteoglycans
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2011
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| Online Access: | http://hdl.handle.net/1721.1/61233 |
| _version_ | 1826192906403184640 |
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| author | Prince, Robin Neely |
| author2 | Douglas A. Lauffenburger and Richard T. Lee. |
| author_facet | Douglas A. Lauffenburger and Richard T. Lee. Prince, Robin Neely |
| author_sort | Prince, Robin Neely |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009. |
| first_indexed | 2024-09-23T09:30:39Z |
| format | Thesis |
| id | mit-1721.1/61233 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T09:30:39Z |
| publishDate | 2011 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/612332022-01-13T07:54:13Z Role of the interaction of proHB-EGF with heparan sulfate proteoglycans Role of the interaction of pro heparin-binding epidermal growth factor-like growth factor with HSPGs Prince, Robin Neely Douglas A. Lauffenburger and Richard T. Lee. Massachusetts Institute of Technology. Dept. of Biological Engineering. Massachusetts Institute of Technology. Department of Biological Engineering Biological Engineering. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009. Cataloged from PDF version of thesis. Includes bibliographical references (p. 106-116). Heparin-binding epidermal growth factor-like growth factor (HB-EGF) exhibits activity as a juxtacrine, paracrine, and autocrine ligand for the epidermal growth factor receptor (EGFR), and possesses the ability to bind heparan sulfate proteoglycans (HSPGs). The interaction of HB-EGF with HSPGs has been previously studied only with the soluble (autocrine/paracrine) form of the protein (sHB-EGF), produced after proteolytic cleavage of the transmembrane form (proHB-EGF) from the cell surface. It was hypothesized that HSPGs interact with proHB-EGF in ways that could alter behavior of the transmembrane form of this ligand and consequent processes. Using an engineered form of proHB-EGF that allowed for independent tracking of the extracellular domain and the C-terminal tail, proHB-EGF was observed primarily at sites of cell-cell contact. However, a dramatic change in this localization was observed upon the addition of exogenous heparin, heparan sulfate, heparinase III or mutation of the heparin-binding domain of proHB-EGF, suggesting that an interaction with HSPGs is responsible for localizing proHB-EGF to sites of cell-cell contact. Further studies in wild-type CHO-Ki cells and heparan sulfate deficient CHOpgsD-677 cells demonstrated that a trans interaction between proHB-EGF and HSPGs on neighboring cells was responsible for this localization. Additionally, this interaction inhibited proteolytic processing of the ligand, as heparin and mutation of the heparin-binding domain increased the amount of sHB-EGF accumulated in the media. by Robin N. Prince. Ph.D. 2011-02-23T14:33:46Z 2011-02-23T14:33:46Z 2009 2009 Thesis http://hdl.handle.net/1721.1/61233 701557801 eng MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission. http://dspace.mit.edu/handle/1721.1/7582 116 p. application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biological Engineering. Prince, Robin Neely Role of the interaction of proHB-EGF with heparan sulfate proteoglycans |
| title | Role of the interaction of proHB-EGF with heparan sulfate proteoglycans |
| title_full | Role of the interaction of proHB-EGF with heparan sulfate proteoglycans |
| title_fullStr | Role of the interaction of proHB-EGF with heparan sulfate proteoglycans |
| title_full_unstemmed | Role of the interaction of proHB-EGF with heparan sulfate proteoglycans |
| title_short | Role of the interaction of proHB-EGF with heparan sulfate proteoglycans |
| title_sort | role of the interaction of prohb egf with heparan sulfate proteoglycans |
| topic | Biological Engineering. |
| url | http://hdl.handle.net/1721.1/61233 |
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