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Protein Kinase B (PKB/Akt), a Key Mediator of the PI3K Signaling Pathway

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Phosphoinositide 3-kinase in Health and Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 346))

Abstract

Protein kinase B (PKB/Akt) is a serine/threonine protein kinase that created serious interest when it was revealed as a mediator of the PI3K pathway. It comprises three isoforms that play both unique and redundant roles. Upon binding to phosphatidylinositol-(3,4,5)-trisphosphate (PIP3) generated by PI3K, PKB is phosphorylated by PDK1 at T308. To achieve full kinase activity, PKB needs to be phosphorylated at a second key residue, S473, by members of the PI3K-related kinase family mTORC2 or DNA-PK, depending on the stimulus and the context. Besides, a number of phosphatases and interacting partners have been shown to further modulate its subcellular localization, phosphorylation, and kinase activity. This review aims at illustrating the remarkable complexity in the regulation of PKB signaling downstream of PI3K. Such regulation could be attributed to the specific roles of the PKB isoforms, their expression pattern, subcellular localization, targets, phosphorylation by upstream kinases in a stimulus- and context-dependent manner and by phosphatases, and interaction with binding partners. This allows this key kinase to fulfill physiological functions in numerous processes, including embryonic development, thymocyte development, adipocyte differentiation, glucose homeostasis, and to avoid pathological loss of control such as tumor formation.

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Acknowledgments

EF is supported by European Molecular Biology Organization (EMBO) Long Term Fellowship (ALTF 506-2005) and Marie-Curie Fellowship (MEIF-CT-2006-025075). AP is supported by the Swiss Cancer League (OCS-01167-09-2001). The Friedrich Miescher Institute for Biomedical research is part of the Novartis Research Foundation.

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  1. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058, Basel, Switzerland

    Elisabeth Fayard, Gongda Xue, Arnaud Parcellier, Lana Bozulic & Brian A. Hemmings

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  1. Elisabeth Fayard
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  2. Gongda Xue
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Correspondence to Brian A. Hemmings .

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  1. Intellikine, North Torreye Pines Road 10931, La Jolla, 92037, California, USA

    Christian Rommel

  2. , Institute of Cancer and the London Schoo, Queen Mary, University of London, Charterhouse Square, London, EC1M 6BQ, United Kingdom

    Bart Vanhaesebroeck

  3. , Dept. Molecular & Exp. Medicine, Scripps Research Institute, N. Torrey Pines Road 10550, La Jolla, 92037, California, USA

    Peter K. Vogt

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Fayard, E., Xue, G., Parcellier, A., Bozulic, L., Hemmings, B.A. (2010). Protein Kinase B (PKB/Akt), a Key Mediator of the PI3K Signaling Pathway. In: Rommel, C., Vanhaesebroeck, B., Vogt, P. (eds) Phosphoinositide 3-kinase in Health and Disease. Current Topics in Microbiology and Immunology, vol 346. Springer, Berlin, Heidelberg. https://doi.org/10.1007/82_2010_58

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