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Bibliographic Record Display

• Author/Creator:Drummond-Barbosa, Daniela.
  
• Title:Requirements for bovine papillomavirus E5-induced mitogenic signaling through the platelet-derived growth factor beta receptor [electronic resource]
  
• Published/Created:1995
  
• Physical Description: 1 online resource (165 p.)
  
• Links:Online thesis
  

• Yale Holdings

  Holdings Record Display

  • Location:Yale Internet Resource
    Information about Off Campus Access
    
    
  • Call Number: None
    
  • Status:No information available 
  • Notes: Online resource
    

   
• Local Notes:Access is available to the Yale community
  
• Notes:Source: Dissertation Abstracts International, Volume: 57-02, Section: B, page: 0849.
  Director: Daniel Christopher DiMaio.
  
• Access and use:Access is restricted by licensing agreement.
• Summary:The bovine papillomavirus type 1 induces hyperproliferation of epithelial cells and dermal fibroblasts during its normal life cycle, and this is reflected by the ability of the BPV genome to induce transformation of fibroblasts in culture. E5 is the primary transforming gene of BPV, and it encodes a very small, highly hydrophobic, and membrane-associated protein which binds to and activates the endogenous platelet-derived growth factor (PDGF) $\beta$ receptor in fibroblasts, leading to morphologic and tumorigenic transformation. I have developed a functional assay to test the ability of PDGF $\beta$ receptor mutants to mediate a mitogenic signal initiated by the BPV E5 protein. Hematopoietic Ba/F3 cells are strictly dependent on interleukin-3 (IL-3) for growth in culture, but co-expression of the wild-type PDGF $\beta$ receptor and the BPV E5 or v-sis protein generated a mitogenic signal which allowed Ba/F3-derived cells to proliferate in the absence of IL-3. In these cells, the BPV E5 protein bound to and caused increased tyrosine phosphorylation of both the mature and the precursor forms of the wild-type PDGF $\beta$ receptor. The tyrosine-kinase activity of the receptor was necessary for BPV E5-induced receptor tyrosine-phosphorylation and mitogenic activity, but not for complex formation with the BPV E5 protein. In contrast, the PDGF-binding domain of the receptor was not required for complex formation with the BPV E5 protein, BPV ES-induced tyrosine phosphorylation or mitogenic activity, demonstrating that receptor activation by the BPV E5 protein is ligand-independent. Analysis of receptor mutants lacking various combinations of tyrosine-phosphorylation sites revealed that the BPV E5 and v-sis proteins display similar requirements for signaling and suggested that the wild-type PDGF $\beta$ receptor can generate multiple independent mitogenic signals. Importantly, these mutants dissociated two activities of the PDGF $\beta$ receptor tyrosine-kinase, both of which are required for sustained mitogenic signaling: (1) receptor autophosphorylation and creation of binding sites for SH2 domain-containing proteins, and (2) phosphorylation of other substrates.
  
• In_:Dissertation Abstracts International 57-02B.
  
• Format:Archives or Manuscripts
• Thesis note:Thesis (Ph.D.)--Yale University, 1995.
  
• Also listed under:Yale University.