Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease
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DOI：
10.2174/1389450116666150416114247
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发表时间：
2016-01-01
影响因子：
3.2
通讯作者：
Klussmann, Enno
中科院分区：
文献类型：
--
作者：
Deak, Veronika A.;Klussmann, Enno
A激酶锚定蛋白（AKAP）通过将cAMP依赖性蛋白激酶A（PKA）拴系到不同的细胞区室来控制PKA的定位。通过与PKA底物和其他信号分子的额外的直接蛋白质-蛋白质相互作用，它们形成多蛋白质复合物。因此，AKAP在时间和空间上调节PKA与其底物的通路，以及cAMP/PKA与其他信号通路的局部串扰。由于越来越多的关于其分子功能和三维结构的信息，以及它们在疾病发展中的新兴作用，AKAP作为潜在的药物靶点成为焦点。靶向AKAP依赖性蛋白质-蛋白质相互作用以干扰细胞内的局部信号处理可能允许开发具有高选择性和较少副作用的治疗剂。
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 protein-protein 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.