Title:Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
Volume: 17
Issue: 10
Author(s): Veronika A. Deák and Enno Klussmann
Affiliation:
Keywords:
AKAP, protein-protein interaction, compartmentalized cAMP signaling, peptide, peptidomimetics, PKA, small
molecules.
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.
