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Title: Activation and inhibition of the Drosophila EGF receptor in development
Author: Howes, R. J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1997
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Multicellular organisms are composed of a wide variety cell types, for example neurons, muscle and epidermal cells. Each cell type is unique, expressing a specific combination of genes that allow them to differentiate their specialised identity. I have examined the role of the argos gene of Drosophila and its function in cell fate determination. I have shown that the argos gene product acts to inhibit the activity of the EGF receptor tyrosine kinase. The EGF receptor has been shown to act through the highly conserved Ras/MAP Kinase pathway and has essential roles in both cell fate determination and cell proliferation. In the visual system the EGF receptor is activated by the TGF-α homologue Spitz. Thus Argos acts to inhibit activation of the receptor by the gene Spitz. This role for argos is unique as it is the first example of an extracellular inhibitor of a receptor tyrosine kinase - a novel method of regulation of this important class of cell surface receptors. I have been trying to understand the mechanism by which argos inhibits the receptor. I have created a series of Argos mutants and have been assaying their ability to act as wild type Argos. For this I have been using an in vivo system utilising the powerful genetics of Drosophila. From the results of this analysis, I have shown that up to half of the amino terminal part of Argos can be removed, yet the protein can still retain Argos activity. Removal of any of the carboxy terminal residues abolishes Argos activity. I have tested the activity of these proteins in vitro using Drosophila tissue culture cells. This system has been used to test for secretion of mutant forms of argos and their bioactivity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available