Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease

Author(s): Veronika A. Deák and Enno Klussmann

Volume 17, Issue 10, 2016

Page: [1147 - 1171] Pages: 25

DOI: 10.2174/1389450116666150416114247

Price: $65

Abstract

A-kinase anchoring proteins (AKAPs) control the localization of cAMP-dependent protein kinase A (PKA) by tethering PKA to distinct cellular compartments. Through additional direct proteinprotein interactions with PKA substrates and other signaling molecules they form multi-protein complexes. Thereby, AKAPs regulate the access of PKA to its substrates in a temporal and spatial manner as well as the local crosstalk of cAMP/PKA with other signaling pathways. Due to the increasing information on their molecular functioning and three-dimensional structures, and their emerging roles in the development of diseases, AKAPs move into the focus as potential drug targets. Targeting AKAP dependent protein-protein interactions for interference with local signal processing inside cells potentially allows for the development of therapeutics with high selectivity and fewer side effects.

Keywords: AKAP, protein-protein interaction, compartmentalized cAMP signaling, peptide, peptidomimetics, PKA, small molecules.


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