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Phosphoinositide 3-kinase in Health and Disease pp 9–29Cite as

PDK1: The Major Transducer of PI 3-Kinase Actions

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

Abstract

Most of the cellular responses to phosphatidylinositol 3-kinase activation and phosphatidylinositol 3,4,5-trisphosphate production are mediated by the activation of a group of AGC kinases comprising PKB, S6K, RSK, SGK and PKC isoforms, which play essential roles in regulating physiological processes related to cell growth, proliferation, survival and metabolism. All these growth-factor-stimulated AGC kinases possess a common upstream activator, namely PDK1, a master kinase, which, being constitutively active, is still able to phosphorylate and activate its AGC substrates in response to rises in the levels of the PtdIns(3,4,5)P3 second messenger. In this chapter, the biochemical, structural and genetic data on the mechanism of action and physiological roles of PDK1 are reviewed, and its potential as a pharmaceutical target for the design of drugs therapeutically beneficial to treat human disease such us diabetes and cancer is discussed.

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Acknowledgements

I am grateful to all the scientists and supporting staff members of the MRC Protein Phosphorylation Unit at the University of Dundee in Scotland, and especially to Professor Dario Alessi, for their help, advice, and all the knowledge and training I received during the 5 years I spent in such a world leading centre. I also thank the Spanish Government Ministerio de Educación y Ciencia (Ramon y Cajal Programme-2006) and Ministerio de Sanidad y Consumo (Project FIS PI070701) for current financial support.

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  1. Institut de Neurociències & Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193, Barcelona, Spain

    José Ramón Bayascas

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  1. José Ramón Bayascas
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Correspondence to José Ramón Bayascas .

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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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Bayascas, J.R. (2010). PDK1: The Major Transducer of PI 3-Kinase Actions. 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_43

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