title: Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase.
abstract: Polo-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 IC(50) 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.
authors.affiliation: ActivX Biosciences, Inc., 11025 North Torrey Pines Road, La Jolla, CA 92037, USA. yongshengl@activx.com
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Liu
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Shreder
authors.forename: Wenzhi
authors.initials: W
authors.lastname: Gai
authors.forename: Sergio
authors.initials: S
authors.lastname: Corral
authors.forename: Douglas K
authors.initials: DK
authors.lastname: Ferris
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Rosenblum
mesh_terms: D000730:Androstadienes / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D019169:Jurkat Cells; D008968:Molecular Conformation; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012235:Rhodamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000077191:Wortmannin; D000097869:Polo-Like Kinase 1
chemical_list: D000730:Androstadienes; D018797:Cell Cycle Proteins; D006576:Heterocyclic Compounds, 4 or More Rings; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D012235:Rhodamines; D000077191:Wortmannin; D000097869:Polo-Like Kinase 1; C502732:AX 7503