Hormonal mechanisms of gene regulation

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Insulin, in addition to controlling our body's use of sugars, controls the metabolism and growth of cells in various tissues. It accomplishes this function by modulating the expression of specific genes. Since the genes are present in the nucleus, and insulin operates by binding to receptors on the cell surface, a cascade of events that transduce the signal from the cell surface in to the nucleus must be activated. This study has been designed to examine specific mediator proteins that form part of this signalling cascade. First, we will be identifying members of a novel pathway of this cascade that is required for activation of MAP kinase, a protein that translocates into the cell nucleus and stimulates gene expression. Second, we will examine ADP-ribosylation. This process is controlled by an enzyme that has not been characterized. Furthermore, it regulates a number of distinct pathways, each associated with a different set of genes. Understanding these two processes will greatly enhance our ability to intervene in this system and eventually allow us to selectively target the negative features of insulin stimulation without interfering with its positive functions.