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Title page for ETD etd-08072007-192935


Type of Document Dissertation
Author Thiel, Kristina Wyatt
URN etd-08072007-192935
Title Analysis of ErbB Receptors: Regulation of ErbB-1 Kinase Activation and Localization of ErbB-4 to Membrane Microdomains
Degree PhD
Department Biochemistry
Advisory Committee
Advisor Name Title
Graham Carpenter Committee Chair
Anne Kenworthy Committee Member
Bruce Carter Committee Member
Charles Sanders Committee Member
Robert Coffey Committee Member
Keywords
  • ErbB-1
  • epidermal growth factor receptor
  • receptor tyrosine kinase
  • lipid rafts
  • detergent-insoluble fraction
  • ErbB-4
  • tumor necrosis factor-alpha converting enzyme
  • Enzyme activation
  • Protein-tyrosine kinase -- Receptors
Date of Defense 2007-08-31
Availability unrestricted
Abstract
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.
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