Wortmannin, a Widely Used Phosphoinositide 3-Kinase Inhibitor, also Potently Inhibits Mammalian Polo-like Kinase
| Autor: | Wenzhi Gai, Sergio Corral, Jonathan S. Rosenblum, Kevin R. Shreder, Douglas K. Ferris, Yongsheng Liu |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Clinical Biochemistry
Molecular Conformation Phosphoinositide 3-kinase inhibitor Cell Cycle Proteins Polo-like kinase Protein Serine-Threonine Kinases Biology Heterocyclic Compounds 4 or More Rings Biochemistry Jurkat cells PLK1 Wortmannin Jurkat Cells 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Proto-Oncogene Proteins Drug Discovery Humans Molecular Biology Phosphoinositide-3 Kinase Inhibitors 030304 developmental biology Pharmacology 0303 health sciences Protein-Serine-Threonine Kinases Rhodamines Kinase General Medicine In vitro 3. Good health Cell biology Androstadienes chemistry 030220 oncology & carcinogenesis Molecular Medicine Protein Kinases |
| Zdroj: | Chemistry & Biology. 12:99-107 |
| ISSN: | 1074-5521 |
| Popis: | SummaryPolo-like kinases (PLKs) play critical roles throughout mitosis. Here, we report that wortmannin, which was previously thought to be a highly selective inhibitor of phosphoinositide (PI) 3-kinases, is a potent inhibitor of mammalian PLK1. Observation of the wortmannin-PLK1 interaction was enabled by a tetramethylrhodamine-wortmannin conjugate (AX7503) that permits rapid detection of PLK1 activity and expression in complex proteomes. Importantly, we show that wortmannin inhibits PLK1 activity in an in vitro kinase assay with an IC50 of 24 nM and when incubated with intact cells. Taken together, our results indicate that, at the concentrations of wortmannin commonly used to inhibit PI 3-kinases, PLK1 is also significantly inhibited. |
| Databáze: | OpenAIRE |
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