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Analysis of ErbB Receptors: Regulation of ErbB-1 Kinase Activation and Localization of ErbB-4 to Membrane Microdomains

The ErbB family of receptor tyrosine kinases regulates cell growth, differentiation, and tumorigenesis. This dissertation contains two independent studies of ErbB-1 and ErbB-4. In one study, the intracellular juxtamembrane region of ErbB-1 was investigated for its role in kinase activation. By creating deletions and mutations in the juxtamembrane region of ErbB-1, the data defined an essential requirement for the juxtamembrane region in the allosteric mechanism of tyrosine kinase activation. The second study focused on proteolytic processing of ErbB-4. Activation of ErbB-4 results in ectodomain and transmembrane domain cleavage events, but the parameters that must be fulfilled to initiate ectodomain proteolysis remain poorly defined. The localization of ErbB-4 and its sheddase to membrane microdomains was evaluated as a regulatory step in sequential proteolytic processing.

Identiferoai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-08072007-192935
Date03 October 2007
CreatorsThiel, Kristina Wyatt
ContributorsGraham Carpenter, Bruce Carter, Robert Coffey, Anne Kenworthy, Charles Sanders
PublisherVANDERBILT
Source SetsVanderbilt University Theses
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.library.vanderbilt.edu/available/etd-08072007-192935/
Rightsunrestricted, I 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 Vanderbilt University 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.

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