The long-term objectives of this study are to explore the potential roles of protein-tyrosine kinases in metazoans and further investigate the molecular mechanisms of their signal transduction pathways using the nematode Caenorhabditis elegans, an experimentally manipulable, model organism. The goals of this proposal are to examine the organismal and subcellular functions of kin-15 and kin-16, tandem C. elegans genes that encode novel transmembrane protein-tyrosine kinases (PTKs) expressed in a subset of the post-embryonic hypodermis (epidermis).
To investigate the organismal function of kin-15 and kin-16, null mutations of each gene will be identified and their mutant phenotype will be characterized at the cellular and organismal levels. In particular, I wish to examine if these PTK genes are required for the regulated pattern of cell fusions that contributes to the post-embryonic development of the large hypodermal syncytium.
To investigate the subcellular function of kin-15 and kin-16, functionally important protein regions will be identified based on the evolutionary conservation of amino acid sequences and the phenotypic effects of in vitro-generated mutations. This analysis should help distinguish between several proposed models for the regulation of kinase activity in these novel PTKs (Morgan and Greenwald, 1993) and provide a basis for further studies.