摘要
通过限定pKa值在不同的细胞区室,A激酶锚定蛋白(AKAPs)控制cAMP依赖的蛋白激酶A(PKA)的定位。通过额外的直接的与PKA的底物的蛋白质之间的相互作用以及与其他信号分子形成多蛋白复合物。因此,以时间和空间的形式以及与其他信号通路的cAMP/PKA的交汇。 AKAPs 以其物质的方式调节了PKA 的通路。由于其分子功能和三维结构信息的增长,还有在疾病发展中的新兴作用,AKAPs作为潜在的药物靶标进入焦点。针对AKAP依赖的蛋白质-蛋白质相互作用干扰细胞内局部信号的处理可能有利于选择性高,副作用少的治疗方法的发展。
关键词: AKAP;蛋白质-蛋白质相互作用;分割的cAMP信号;信号肽;模拟物;PKA;小分子。
Current Drug Targets
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:
关键词: AKAP;蛋白质-蛋白质相互作用;分割的cAMP信号;信号肽;模拟物;PKA;小分子。
摘要: 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.
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Cite this article as:
Veronika A. Deák and Enno Klussmann , Pharmacological Interference With Protein-protein Interactions of Akinase Anchoring Proteins as a Strategy for the Treatment of Disease, Current Drug Targets 2016; 17 (10) . https://dx.doi.org/10.2174/1389450116666150416114247
DOI https://dx.doi.org/10.2174/1389450116666150416114247 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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