A central question in biology is the regulation of the expression of cellular genes by the environmental signals a cell receives. This signal-response process is the basis for many biological functions including cell differentiation, cell proliferation as well as the formation of long term memory. A recent advancement in the understanding of this signal-response process is the recognition that activators of the cyclic AMP- dependent protein kinase and protein kinase C can regulate gene expression. Because protein kinases are in general regulated by second messengers, which are synthesized in response to environmental signals, the demonstration of a connection between protein kinases and gene expression provides clues to a better understanding of this signal-response process. The goal of this proposal is to understand in particular the role of a tyrosine- specific protein kinase in the regulation of gene expression. A system has been developed using temperature sensitive mutants of the v-abl tyrosine kinase to examine the mechanism of regulation of gene expression. A strategy has been out to clone genes that are regulated by the v-abl tyrosine kinase, and we have identified at least one cellular gene whose expression can be induced by the v-abl tyrosone kinase. Experiments will be performed to determines the site of action of the v-abl tyrosine kinase and to elucidate the pathway linking this kinase to the expression of cellular genes. This research will shed light on the mechanism by which the v-abl tyrosine kinase regulates gene expression and it will contribute to the understanding of a central biological signal-response process.
