MECHANISMS AND ROLES OF PDK1 IN INSULIN SIGNALING

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DESCRIPTION: (Adapted from the applicant's abstract) The long-term goal of the research is to elucidate the molecular and biochemical mechanisms of insulin receptor signal transduction and regulation. In the proposed study, the investigator is focusing on a newly identified serine/threonine kinase, the phosphoinositide-dependent protein kinase 1 (PDK1). Whereas some evidence suggests that PDK1 may play an important part in insulin action, the regulatory mechanisms and the exact role of the enzyme in the signaling process are still unknown. In the proposed studies, the investigator will determine whether PDK1 is regulated by mechanisms such as phosphorylation and oligomerization. The investigator will investigate whether PDK1 is an upstream kinase for protein kinase N (PKN), a serine/threonine protein kinase that has been implicated in insulin action. He will examine the potential roles of PDK1 in insulin-mediated biological events such as glycogen synthesis, glucose transport and protein synthesis. He will test whether PDK1 exerts its role in insulin signaling processes by activation of atypical protein kinase C isoforms and PKN. Results from these studies should provide useful information on the physiological importance of PDK1 in insulin signaling and add to our understanding of insulin resistance, a primary cause of type II diabetes.