Direct AKAP-mediated protein-protein interactions as potential drug targets

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Item Type:	Review
Title:	Direct AKAP-mediated protein-protein interactions as potential drug targets
Creators Name:	Hundsrucker, C. and Klussmann, E.
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.
Keywords:	A Kinase Anchor Proteins, Drug Delivery Systems, Protein Binding, Proteins, Signal Transduction, Animals
Source:	Handbook of Experimental Pharmacology
ISSN:	0171-2004
Publisher:	Springer
Volume:	186
Page Range:	483-503
Date:	2008
Official Publication:	https://doi.org/10.1007/978-3-540-72843-6_20
PubMed:	View item in PubMed

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