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Int. J. Mol. Sci. 2008, 9(11), 2217-2230; doi:10.3390/ijms9112217
Review

Contribution of Natural Inhibitors to the Understanding of the PI3K/PDK1/PKB Pathway in the Insulin-mediated Intracellular Signaling Cascade

1
 and 2,*
Received: 15 July 2008; in revised form: 8 November 2008 / Accepted: 12 November 2008 / Published: 12 November 2008
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Abstract: The critical initial steps in insulin action include phosphorylation of adapter proteins and activation of phosphatidylinositol 3-kinase (PI3K). One of important components in this process is a protein called Akt/protein kinase B (PKB). The work of numerous different researchers indicates a role of PKB in regulating insulin-stimulated glucose uptake. The crucial role of lipid second messengers in PKB activation has been dissected through the use of the PI3K-specific inhibitors wortmannin and LY294002. Receptor-activated PI3K synthesizes the lipid second messenger PtdIns[3,4,5]-trisphosphate, leading to the recruitment of PKB to the membrane. Membrane attachment of PKB is mediated by its pleckstrin homology domain binding to PtdIns[3,4,5]-trisphosphate or PtdIns[3,4]-bisphosphate with high affinity. Activation of PKB alpha is then achieved at the plasma membrane by phosphorylation of Thr308 in the activation-loop of the kinase domain and Ser473 in the carboxy-terminal regulatory region, respectively. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) is responsible for T308 phosphorylation. The usage of specific inhibitors and natural compound has significantly contributed to investigate the molecular mechanism of PI3K/PDK1/PKB signaling pathway, leading to the putative therapeutics benefits of patients. This review focuses on the contribution of natural inhibitor or compound in our understanding of the mechanism by which insulin induces, especially in PI3K/ PDK1/PKB signaling.
Keywords: Diabetes mellitus; phosphatidylinositol 3-kinase; 3-Phosphoinositide-dependent protein kinase-1; protein kinase B; natural inhibitors Diabetes mellitus; phosphatidylinositol 3-kinase; 3-Phosphoinositide-dependent protein kinase-1; protein kinase B; natural inhibitors
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Cho, J.Y.; Park, J. Contribution of Natural Inhibitors to the Understanding of the PI3K/PDK1/PKB Pathway in the Insulin-mediated Intracellular Signaling Cascade. Int. J. Mol. Sci. 2008, 9, 2217-2230.

AMA Style

Cho JY, Park J. Contribution of Natural Inhibitors to the Understanding of the PI3K/PDK1/PKB Pathway in the Insulin-mediated Intracellular Signaling Cascade. International Journal of Molecular Sciences. 2008; 9(11):2217-2230.

Chicago/Turabian Style

Cho, Jae Y.; Park, Jongsun. 2008. "Contribution of Natural Inhibitors to the Understanding of the PI3K/PDK1/PKB Pathway in the Insulin-mediated Intracellular Signaling Cascade." Int. J. Mol. Sci. 9, no. 11: 2217-2230.



Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert