Receptor tyrosine kinases are important regulatory proteins that control many aspects of cellular metabolism, growth, and differentiation. Many extracellular signaling molecules are known to exert their effects on cell regulation by binding to these receptors. The ultimate objective of the proposed research is to understand the molecular mechanisms that receptor tyrosine kinases use to regulate cellular behavior. This could provide important insights into how these cellular processes are regulated and coordinated, and how inappropriate activation of receptor tyrosine kinases can lead to neoplastic transformation of cells. In order to address this question, we study the differentiation of a photoreceptor cell in the Drosophila eye that is regulated by a receptor tyrosine kinase, the product of the sevenless gene. Activation of the sevenless receptor results in a single cell to develop as a photoreceptor rather than a non-neuronal cell. The product of another gene, sina, is required in this cell to make the same developmental choice. Thus sina may act directly to regulate gene expression during photoreceptor differentiation. The action of sina on photoreceptor development is dependent on activation of the sevenless receptor. Regulation of sina by signals mediated by sevenless is most likely achieved through stimulation of the activity of sina protein. In order to identify molecules that interact with sina, we isolated mutations that attenuate sina activity and found nine genes (called Enhancers of sina) that are candidates to encode such molecules. Of these nine, three genes appear to act in the sevenless signaling pathway.
The aims of the proposed research are to: (1) biochemically characterize sina protein and ask what in vitro activities account for its genetic activities; (2) genetically identify more genes that interact with sina and act in sevenless signal transduction; (3) characterize at the molecular level these genes and those that were previously identified.
