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EGFR Activation by Spatially Restricted Ligands

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Annual summary rept. 1 Jun 2004-31 May 2005

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Misregulation of Transforming Growth Factor alpha TGFalpha and increased Epidermal Growth Factor Receptor EGFR activity has been associated with an increased prognosis of breast cancer. During oogenesis in Drosophila melanogaster, local EGFR activation by the spatially restricted TGF alpha-like ligand, Gurken Grk, is required for axis formation in the egg and future embryo. Squid, a heterogeneous nuclear ribonucleoprotein hnRNP functions in the localization and translational regulation of grk mRNA. The purpose of this project is to identify factors that function with Squid to produce spatially-restricted EGFR activation. I have identified an arginine methyltransferase CG6554 that interacts with Squid, but mutations in this enzyme do not produce a phenotype. I have gathered evidence that Squid is methylated on arginine residues. This methylation could function to mediate Squids different roles in regulating Grk expression. I generated several Squid transgenes in which the potential methylation sites have been mutated. Characterization of these transgenes should allow us to elucidate the function of Squid methylation and its role in the regulation of Grk expression. These factors, which interact with Squid to control Grk expression, could define potential causes of EGFR misregulation that result in human breast cancer, and they may provide possible targets for drug development.

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  • Biology
  • Medicine and Medical Research

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