{"id":{"repo_id":"mit","oai_identifier":"oai:dspace.mit.edu:1721.1/61233"},"canonical_url":"https://search.dev.ndltd.org/etd/mit/oai:dspace.mit.edu:1721.1/61233","repository":{"repo_id":"mit","name":"MIT","base_url":"https://dspace.mit.edu/oai/request"},"display":{"title":"Role of the interaction of proHB-EGF with heparan sulfate proteoglycans","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Prince, Robin Neely"],"institution":"Massachusetts Institute of Technology","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":"Massachusetts Institute of Technology. Department of Biological Engineering","school":null,"contributors":[],"advisors":["Douglas A. Lauffenburger and Richard T. Lee."],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-22T22:21:02Z","subjects":["Biological Engineering."],"languages":["eng"],"rights":["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."],"rights_urls":["http://dspace.mit.edu/handle/1721.1/7582"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/1721.1/61233","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Douglas A. Lauffenburger and Richard T. Lee."]},{"key":"dc:contributor.department","label":"Department","values":["Massachusetts Institute of Technology. Department of Biological Engineering"]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Massachusetts Institute of Technology. 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They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission."]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://dspace.mit.edu/handle/1721.1/7582"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1721.1/61233"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009.","Cataloged from PDF version of thesis.","Includes bibliographical references (p. 106-116)."]},{"key":"dc:description.abstract","label":"Abstract","values":["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."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Ph.D."]},{"key":"dc:title","label":"Title","values":["Role of the interaction of proHB-EGF with heparan sulfate proteoglycans"]}]}],"canonical_facts":{"dc:contributor.advisor":["Douglas A. Lauffenburger and Richard T. Lee."],"dc:contributor.department":["Massachusetts Institute of Technology. Department of Biological Engineering"],"dc:contributor.other":["Massachusetts Institute of Technology. Dept. of Biological Engineering."],"dc:creator":["Prince, Robin Neely"],"dc:date.accessioned":["2011-02-23T14:33:46Z"],"dc:date.available":["2011-02-23T14:33:46Z"],"dc:date.issued":["2009"],"dc:description":["Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biological Engineering, 2009.","Cataloged from PDF version of thesis.","Includes bibliographical references (p. 106-116)."],"dc:description.abstract":["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."],"dc:description.degree":["Ph.D."],"dc:identifier.uri":["http://hdl.handle.net/1721.1/61233"],"dc:language.iso":["eng"],"dc:publisher":["Massachusetts Institute of Technology"],"dc:rights":["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."],"dc:rights.uri":["http://dspace.mit.edu/handle/1721.1/7582"],"dc:subject":["Biological Engineering."],"dc:title":["Role of the interaction of proHB-EGF with heparan sulfate proteoglycans"],"dc:type":["Thesis"]},"updated_at":"2026-07-22T22:21:02Z"}