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.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Endocrinology Study Section (END)
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Blondel, Olivier
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University of Texas Health Science Center San Antonio
Other Domestic Higher Education
San Antonio
United States
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Wang, Changhua; Liu, Meilian; Riojas, Ramon A et al. (2009) Protein kinase C theta (PKCtheta)-dependent phosphorylation of PDK1 at Ser504 and Ser532 contributes to palmitate-induced insulin resistance. J Biol Chem 284:2038-44
Kikani, Chintan K; Dong, Lily Q; Liu, Feng (2005) ""New""-clear functions of PDK1: beyond a master kinase in the cytosol? J Cell Biochem 96:1157-62
Dong, Lily Q; Liu, Feng (2005) PDK2: the missing piece in the receptor tyrosine kinase signaling pathway puzzle. Am J Physiol Endocrinol Metab 289:E187-96
Lim, Mei Ann; Yang, Linda; Zheng, Yi et al. (2004) Roles of PDK-1 and PKN in regulating cell migration and cortical actin formation of PTEN-knockout cells. Oncogene 23:9348-58
Stratford, Suzanne; Hoehn, Kyle L; Liu, Feng et al. (2004) Regulation of insulin action by ceramide: dual mechanisms linking ceramide accumulation to the inhibition of Akt/protein kinase B. J Biol Chem 279:36608-15
Lim, Mei A; Riedel, Heimo; Liu, Feng (2004) Grb10: more than a simple adaptor protein. Front Biosci 9:387-403
Wick, Michael J; Ramos, Fresnida J; Chen, Hui et al. (2003) Mouse 3-phosphoinositide-dependent protein kinase-1 undergoes dimerization and trans-phosphorylation in the activation loop. J Biol Chem 278:42913-9
Lim, Mei A; Kikani, Chintan K; Wick, Michael J et al. (2003) Nuclear translocation of 3'-phosphoinositide-dependent protein kinase 1 (PDK-1): a potential regulatory mechanism for PDK-1 function. Proc Natl Acad Sci U S A 100:14006-11
Dong, Lily Q; Ramos, Fresnida J; Wick, Michael J et al. (2002) Cloning and characterization of a testis and brain-specific isoform of mouse 3'-phosphoinositide-dependent protein kinase-1, mPDK-1 beta. Biochem Biophys Res Commun 294:136-44
Wick, Michael J; Wick, KeriLyn R; Chen, Hui et al. (2002) Substitution of the autophosphorylation site Thr516 with a negatively charged residue confers constitutive activity to mouse 3-phosphoinositide-dependent protein kinase-1 in cells. J Biol Chem 277:16632-8

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