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Direct AKAP-Mediated Protein-Protein Interactions as Potential Drug Targets

  • Chapter
Protein-Protein Interactions as New Drug Targets

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

Abstract

A-kinase-anchoring proteins (AKAPs) are a diverse family of about 50 scaffolding proteins. They are defined by the presence of a structurally conserved protein kinase A (PKA)-binding domain. AKAPs tether PKA and other signalling proteins such as further protein kinases, protein phosphatases and phosphodiesterases by direct protein-protein interactions to cellular compartments. Thus, AKAPs form the basis of signalling modules that integrate cellular signalling processes and limit these to defined sites. Disruption of AKAP functions by gene targeting, knockdown approaches and, in particular, pharmacological disruption of defined AKAP-dependent protein-protein interactions has revealed key roles of AKAPs in numerous processes, including the regulation of cardiac myocyte contractility and vasopressin-mediated water reabsorption in the kidney. Dysregulation of such processes causes diseases, including cardiovascular and renal disorders. In this review, we discuss AKAP functions elucidated by gene targeting and knockdown approaches, but mainly focus on studies utilizing peptides for disruption of direct AKAP-mediated protein-protein interactions. The latter studies point to direct AKAP-mediated protein-protein interactions as targets for novel drugs.

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Abbreviations

AKAP:

A-kinase-anchoring protein

AVP:

arginine-vasopressin

GEF:

guanine nucleotide exchange factor

PKA:

protein kinase A

SR:

sarcoplasmic reticulum

PDE:

phosphodiesterase

cAMP:

cyclic adenosine monophosphate

PLN:

phospholamban

RyR2:

ryanodinereceptorstype2

PP2B:

protein phosphatase 2B/ calcineurin

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Authors and Affiliations

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

    C. Hundsrucker & E. Klussmann

  2. Institut für Pharmakologie, Charité—Universitätsmedizin, Freie Universität Berlin, Berlin, Germany

    E. Klussmann

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  1. C. Hundsrucker
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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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© 2008 Springer-Verlag Berlin Heidelberg

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Hundsrucker, C., Klussmann, E. (2008). Direct AKAP-Mediated Protein-Protein Interactions as Potential Drug Targets. 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_20

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