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dc.contributor.authorDrahos, Karen Elizabethen_US
dc.date.accessioned2014-03-14T20:33:09Z
dc.date.available2014-03-14T20:33:09Z
dc.date.issued2009-03-23en_US
dc.identifier.otheretd-04042009-232708en_US
dc.identifier.urihttp://hdl.handle.net/10919/31626
dc.description.abstractThrombosis, the major cause of heart attack and strokes,1 is triggered by localized clotting of the blood as the result of deregulated platelet aggregation. During the repair of vascular injury, clotting usually occurs when platelets adhere to each other at the site of vascular injury in order to stop bleeding.2 Distinct protein receptors and adhesive ligands together with the blood flow conditions govern this process. One of the negative regulators in platelet aggregation is Disabled-2 (Dab2), a modular protein that is released upon platelet activation to the extracellular platelet surface.3 Dab2 inhibits platelet aggregation through its phosphotyrosine-binding (PTB) domain by competing with fibrinogen for ï ¡IIï ¢3 integrin binding on the activated platelet surface.3 Sulfatides are also found on the platelet surface,4 interacting with adhesive and coagulation proteins5-7 and, thus, they are thought to play a major role in haemostasis and thrombogenesis. Here, we show that the Dab2 PTB domain specifically interacts with sulfatides through two conserved basic motifs. The sulfatide-binding site overlaps with that of phosphatidylinositol 4,5-biphosphate (PtdIns(4,5)P2) in the PTB domain. Whereas sulfatides recruit the Dab2 PTB domain to the platelet surface, thus sequestering the protein from thrombin-mediated platelet aggregation, the phosphoinositide mediates its internalization. Experimental data support the hypothesis that two pools of Dab2 co-exist at the platelet surface and that the balance between them controls the extent of the clotting response.en_US
dc.publisherVirginia Techen_US
dc.relation.haspartDrahos_THESIS_051309.pdfen_US
dc.rightsI hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Virginia Tech or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.en_US
dc.subjectplateletsen_US
dc.subjectendocytosisen_US
dc.subjectDisabled-2en_US
dc.subjectsulfatidesen_US
dc.titleSulfatides mediate Disabled-2 membrane localization and stability during platelet aggregation.en_US
dc.typeThesisen_US
dc.contributor.departmentBiologyen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
dc.contributor.committeechairFinkielstein, Carla V.en_US
dc.contributor.committeememberCapelluto, Daniel G. S.en_US
dc.contributor.committeememberSible, Jill C.en_US
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-04042009-232708/en_US
dc.date.sdate2009-04-04en_US
dc.date.rdate2009-08-03
dc.date.adate2009-05-14en_US


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