The focus of this proposal is the tyrosine kinase, hck (hematopoietic cell kinase) expressed primarily in cells of the myloid lineage. Its relationship to the src family of tyrosine kinase is established based on homology at the level of DNA sequence. One of the specific aims in the proposal is to establish that this protein has tyrosine kinase activity. Experiments have been designed to test for autophosphorylation as well as phosphorylation of other substrates. The second specific aim is to examine possible functions of the hck protein. Based on our knowledge of functions associated with tyrosine kinases, we have proposed a series of experiments to examine the possible role of hck in the transformation, growth or activation of macrophages. Using constructions that either express sense or antisense RNA for hck we will respectively over express or block the expression of hck in normal macrophages or selected macrophage-like cell lines. If we can demonstrate that hck is able to transform cells, this tyrosine kinase may serve as a suitable model for future studies of transformation within the hematopoietic lineage. The long-term objectives of this project are to define the role of hck in normal macrophage function and to use this information as a means of possibly modulating macrophage growth or function within the immune response. The association of hck expression with cells in the hematopoietic lineage may prove to be an interesting model for our studies on the regulation of the immune system.
