Dissemin is shutting down on January 1st, 2025

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Elsevier, Seminars in Cell and Developmental Biology, 2(15), p. 161-170, 2004

DOI: 10.1016/j.semcdb.2003.12.022

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PDK1, the master regulator of AGC kinase signal transduction

Journal article published in 2004 by Alfonso Mora, David Komander, Daan M. F. van Aalten ORCID, Dario R. Alessi ORCID
This paper is available in a repository.
This paper is available in a repository.

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Abstract

The interaction of insulin and growth factors with their receptors on the outside surface of a cell, leads to the activation of phosphatidylinositol 3-kinase (PI 3-kinase) and generation of the phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) second messenger at the inner surface of the cell membrane. One of the most studied signalling events controlled by PtdIns(3,4,5)P3, comprises the activation of a group of AGC family protein kinases, including isoforms of protein kinase B (PKB)/Akt, p70 ribosomal S6 kinase (S6K), serum- and glucocorticoid-induced protein kinase (SGK) and protein kinase C (PKC), which play crucial roles in regulating physiological processes relevant to metabolism, growth, proliferation and survival. Here, we review recent biochemical, genetic and structural studies on the 3-phosphoinositide-dependent protein kinase-1 (PDK1), which phosphorylates and activates the AGC kinase members regulated by PI 3-kinase. We also discuss whether inhibitors of PDK1 might have chemotherapeutic potential in the treatment of cancers in which the PDK1-regulated AGC kinases are constitutively activated.