Signal Transduction by the EGF Receptor in Normal and Transformed Cells: a Dissertation

Publication Date

December 1996

Document Type

Doctoral Dissertation


Graduate School of Biomedical Sciences, Department of Molecular Genetics & Microbiology


Receptor, Epidermal Growth Factor; Signal Transduction; Academic Dissertations


Much research has been conducted and significant progress has been made in understanding how signals are transmitted in response to extracellular stimuli. Continued research is necessary to elucidate how specificity in signaling from the cell surface is achieved and to understand how disruption of such signaling pathways leads to disease. The question of specificity is important since many of the same proteins can be activated by different stimuli in a variety of signaling pathways. One means of achieving specificity would be for different cell types to express different sets of proteins that interact with "common" proteins such as GRB2, Shc, and Ras. There were two goals to my dissertation research. The first goal was to study disease which results from perturbation of the EGF receptor. The second was to explore the possibility that signals generated in response to EGF or other stimuli might be transmitted through MAP kinase proteins other than ERKs 1 and 2.

Chapter II of this thesis centers around further analyzing the disease potential of erbB in chickens. I have conducted oncogenicity tests with an erbB oncogene that contains no mutations, only the characteristic N-terminal truncation. My studies have revealed that truncation of the EGF receptor (erbB) can induce tumorigenesis of the kidney as well as the erythroblastosis originally associated with erbB. Previous studies have only found kidney tumors in association with mutated forms of the erbB oncogene. Furthermore, I have demonstrated that mutational removal of a negative regulatory serine phosphorylation site increases the number of wing web tumors caused by the erbB oncogene.

Chapter III describes the identification of the Ser/Thr protein kinase p56 KKIAMRE and characterization of p56 KKIAMRE and p42 KKIALRE. These kinases have homology to the MAP kinase group and contain the conserved Thr-Xaa-Tyr dual phosphorylation site. I have demonstrated that both kinases can be activated by treatment of cells with EGF. Interestingly, phosphorylation of Thr and Tyr in the Thr-Xaa-Tyr motif is not necessary for EGF stimulated activity.


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