Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
Sci Rep. 2022 Jul 29;12(1):13015. doi: 10.1038/s41598-022-16557-w.
Kinase inhibitors often exert on/off-target effects, and efficient data analysis is essential for assessing these effects on the proteome. We developed a workflow for rapidly performing such a proteomic assessment, termed as kinase inhibitor proteome impact analysis (KOPI). We demonstrate KOPI's utility with staurosporine (STS) on the leukemic K562 cell proteome. We identified systematically staurosporine's non-kinome interactors, and showed for the first time that it caused paradoxical hyper- and biphasic phosphorylation.
激酶抑制剂通常会产生脱靶效应,因此高效的数据分析对于评估其对蛋白质组的影响至关重要。我们开发了一种快速进行这种蛋白质组评估的工作流程,称为激酶抑制剂蛋白质组影响分析 (KOPI)。我们用 STS 对白血病 K562 细胞蛋白质组进行了 KOPI 的实用性验证。我们系统地鉴定了 STS 的非激酶相互作用物,并首次表明它会导致反常的超磷酸化和双相磷酸化。