Tyrosine kinases are important regulatory molecules in the regulation of normal growth and differentiation and in the induction of aberrant growth properties by tyrosine kinase oncogenes. The goal of this proposal is to define how one particular tyrosine kinase, the Abelson proto-oncogene homolog of Drosophila, is regulated and to define the substrate macromolecules through which the tyrosine kinase activity modulates events in the cell. The advantage of studying the Abelson tyrosine kinase either as regulators or as substrates, or as other components in a regulatory pathway that functions during the normal growth and development of the organism. The pathway on which the Drosophila Abelson tyrosine kinase functions is required for the proper terminal differentiation and/or patterning of phenotypes caused by lesions in the Drosophila genes by suppression of specific lesions introduced into the kinase interacts with other proteins (e.g., regulatory factors and substrates) in mammalian cells should be suggested by our work in Drosophila. Eventually mammalian DNAs encoding regulatory proteins or substrates for a mammalian Abelson tyrosine kinase might be isolated directly by DNA hybridization under low stringency conditions using as probes DNA from the Drosophila genes identified in our studies. This information may be useful in understanding molecular mechanisms of transformation in that the Abelson tyrosine kinase is the activated oncoprotein both in mouse pre-B cell leukemias induced by Abelson murine leukemia virus and in some human leukemias including chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). Identification of the genes that genetically interact with the Abelson product will provide the first clues to the biochemical processes that are modulated by the Abelson tyrosine kinase.
