Department of Pharmacology, University of Washington, Seattle, WA, 98195, USA.
Department of Pharmacology, University of Washington, Seattle, WA, 98195, USA.
Trends Pharmacol Sci. 2020 Dec;41(12):933-946. doi: 10.1016/j.tips.2020.09.007. Epub 2020 Oct 17.
Regulatory enzymes often have different roles in distinct subcellular compartments. Yet, most drugs indiscriminately saturate the cell. Thus, subcellular drug-delivery holds promise as a means to reduce off-target pharmacological effects. A-kinase anchoring proteins (AKAPs) sequester combinations of signaling enzymes within subcellular microdomains. Targeting drugs to these 'signaling islands' offers an opportunity for more precise delivery of therapeutics. Here, we review mechanisms that bestow protein kinase A (PKA) versatility inside the cell, appraise recent advances in exploiting AKAPs as platforms for precision pharmacology, and explore the impact of methodological innovations on AKAP research.
调节酶在不同的亚细胞隔室中通常具有不同的作用。然而,大多数药物不加区分地使细胞饱和。因此,亚细胞药物输送有望成为减少非靶标药理作用的手段。蛋白激酶 A(PKA)锚定蛋白(AKAPs)将信号酶组合隔离在亚细胞微域内。将药物靶向这些“信号岛”为更精确地递送电疗药物提供了机会。在这里,我们回顾了赋予细胞内蛋白激酶 A(PKA)多功能性的机制,评估了利用 AKAP 作为精准药理学平台的最新进展,并探讨了方法创新对 AKAP 研究的影响。