Analysis of the Drosophila Gene Rhomboid

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0094634BierDr. Bier intends to study the role of a multi-pass integral membrane protein known as Rhomboid (Rho) in promoting signaling via the Epidermal Growth Factor Receptor (EGF-R) in the fruit fly Drosophila melanogaster. The EGF-R is a member of the widely used receptor tyrosine kinase (RTK) family, which activates the RAS/MAP-Kinase pathway. Rhomboid functions in conjunction with a single pass transmembrane protein (Star) to activate EGF-R signaling by a mechanism involving the production of a diffusible extracellular signal. The specific goals of this project are to: 1) analyze the function of domains of Rho that are predicted to lie inside or outside of the cell, 2) examine the basis for the intimate interaction between Rho and Star in promoting EGF-R signaling, and 3) determine whether Rho and Star participate directly or indirectly in producing a diffusible EGF-like signal. Dr. Bier anticipates that this study will lead to the formulation of specific mechanistic models for how Rho and Star activate EGF-ligands. More generally, this project should broaden our understanding of fundamental mechanisms for regulating the production and range of action of RTK ligands during development. Since RTK signaling pathways play a central role in development and regulation of cellular proliferation in vertebrates and invertebrates alike, these insights should have general implications for understanding cell-cell communication, which is also highly