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Protein-Protein Interactions as New Drug Targets pp 185–203Cite as

Protein Scaffolds, Lipid Domains and Substrate Recognition in Protein Kinase C Function: Implications for Rational Drug Design

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 186))

Abstract

Protein kinase C (PKC) represents a family of lipid-regulated protein kinases with ubiquitous expression throughout the animal kingdom. High fidelity in PKC phosphorylation of intended target substrates is crucial for normal cell and tissue function. Therefore, it is likely that multiple interdependent factors contribute to determining substrate specificity in vivo, including divalent cation binding, substrate recognition motifs, local lipid heterogeneity and protein scaffolds. This review provides an overview of targeting mechanisms for the three subclasses of PKC isoforms, conventional, novel and atypical, with an emphasis on how they bind to substrates, lipids/lipid microdomains and multifunctional protein scaffolds. The diversity of interactions between PKC isoforms and their immediate environment is extensive, suggesting that systems biology approaches including proteomics and network modeling may be important strategies for rational drug design in the future.

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  1. Department of Physiology, Director of Human Proteomics Program, University of Wisconsin, 1300 University Avenue, Madison, WI, 53706, USA

    J. W. Walker

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  1. Leibniz-Institut für Molekulare Pharmakologie, Robert-Rössle-Str. 10, 13125, Berlin, Germany

    Enno Klussmann

  2. The Vollum Institute, Oregon Health & Science University, Medical Research Bldg, Rm 322D 3181 SW Sam Jackson Park Road, Portland, OR, 97239-3098, USA

    John Scott Ph.D.

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Walker, J.W. (2008). Protein Scaffolds, Lipid Domains and Substrate Recognition in Protein Kinase C Function: Implications for Rational Drug Design. In: Klussmann, E., Scott, J. (eds) Protein-Protein Interactions as New Drug Targets. Handbook of Experimental Pharmacology, vol 186. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-72843-6_8

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