MULTICOLOR MONITORING OF DYSREGULATED PROTEIN KINASES IN CHRONIC MYELOGENOUS LEUKEMIA
作者： Qunzhao Wang , Eric I. Zimmerman , Alexei Toutchkine , Timothy D. Martin , Lee M. Graves
DOI: 10.1021/CB100099H
关键词:
摘要: The Bcr-Abl and Lyn protein tyrosine kinases have been separately linked to the emergence of imatinib resistance in patients with chronic myelogenous leukemia. We developed fluorescent sensors for these that are enzymatically photophysically distinct, allowing us simultaneously, yet separately, visualize kinase activities both Abl Lyn. Multicolor monitoring revealed an imatinib-resistant cell line (MYL-R) displays a remarkable 13-fold enhancement activity relative its imatinib-sensitive counterpart (MYL). By contrast, lines display nearly identical activities. upregulation phosphotransferase MYL-R cells is overexpression B isoform. Furthermore, possess 4-fold higher level activated 5-fold lower autoinhibited than MYL cells. Finally, studies activating SH2 ligand from primed act...
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