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Protein Kinase C Protocols pp 171–189Cite as

PDK-1 and Protein Kinase C Phosphorylation

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Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 233))

Abstract

The discovery of the phosphoinositide-dependent kinase-1 (PDK-1) as the upstream kinase for protein kinase C (PKC) represented an important step in the understanding of the regulation of this crucial lipid-signaling enzyme. Three laboratories simultaneously described PDK-1 as the activation loop upstream kinase for conventional (PKCα and PKCβII; ref. 1), novel (PKCδ and PKCε ref. 2), and atypical (PKCζ refs. 2 and 3) isozymes. It is now well established that PDK-1 is the upstream kinase for all PKC family members, and numerous studies have addressed the detailed biochemical mechanisms by which PDK-1 phosphorylates PKC thereby regulating its function in cells (for reviews, see refs. 4–6). PDK-1 phosphorylates PKCs at a critical Thr residue in the so-called activation loop sequence of the highly conserved catalytic kinase domain (see Chapter 13), and this event is required for PKC to gain catalytic competency. Phosphorylation of the activation loop Thr correctly aligns residues within the active site and this permits transfer of the gamma phosphate of ATP to an exogenous substrate. This phosphorylation triggers two phosphorylations at the carboxyl-terminus required to stabilize the catalytically competent species of PKC. Therefore, phosphorylation is a rate-limiting step in the regulation of PKC and precedes other regulatory events, including binding of lipid activators (7).

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Author information

Authors and Affiliations

  1. Department of Pathology, Beth Israel Deaconess Medical School, Harvard Medical School, Boston, MA

    Alex Toker

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  1. Alex Toker
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Editor information

Editors and Affiliations

  1. Department of Pharmacology, University of California at San Diego, La Jolla, CA

    Alexandra C. Newton

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© 2003 Humana Press Inc., Totowa, NJ

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Toker, A. (2003). PDK-1 and Protein Kinase C Phosphorylation. In: Newton, A.C. (eds) Protein Kinase C Protocols. Methods in Molecular Biology™, vol 233. Humana Press. https://doi.org/10.1385/1-59259-397-6:171

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  • DOI: https://doi.org/10.1385/1-59259-397-6:171

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-068-7

  • Online ISBN: 978-1-59259-397-2

  • eBook Packages: Springer Protocols

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