Subcellular drug targeting illuminates local kinase action
作者: Paula J BuckoChloe K LombardLindsay RathbunIrvin GarciaAkansha BhatLinda WordemanF Donelson SmithDustin J MalyHeidi HehnlyJohn D Scott
作者单位: 11 Department of Pharmacology University of Washington Seattle United States
22 Department of Chemistry University of Washington Seattle United States
33 Department of Biology Syracuse University Syracuse United States
44 Department of Physiology and Biophysics University of Washington Seattle United States
刊名: eLife, 2019, Vol.8
来源数据库: eLife Sciences Publications, Ltd
DOI: 10.7554/eLife.52220
关键词: KinasesLocal signalingMitosis
原始语种摘要: Deciphering how signaling enzymes operate within discrete microenvironments is fundamental to understanding biological processes. A-kinase anchoring proteins (AKAPs) restrict the range of action of protein kinases within intracellular compartments. We exploited the AKAP targeting concept to create genetically encoded platforms that restrain kinase inhibitor drugs at distinct subcellular locations. Lo cal K inase I nhibition ( LoKI ) allows us to ascribe organelle-specific functions to broad specificity kinases. Using chemical genetics, super resolution microscopy, and live-cell imaging we discover that centrosomal delivery of Polo-like kinase 1 (Plk1) and Aurora A (AurA) inhibitors attenuates kinase activity, produces spindle defects, and prolongs mitosis. Targeted inhibition of Plk1 in...
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  • targeting 导向目标
  • proteins 蛋白质
  • kinase 激酶
  • genetic 遗传的
  • distinct 相异的
  • together 共同
  • action 行为
  • kinetochore 着丝粒
  • local 局部的
  • within 在以内