Polo-like kinase 1-mediated phosphorylation of the GTP-binding protein Ran is important for bipolar spindle formation |
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Authors: | Feng Yang Yuan Jin Hui Maloid Sharon C Fisher Rebecca Copeland Terry D Longo Dan L Conrads Thomas P Veenstra Timothy D Ferris Andrea Hughes Steve Dimitrov Dimiter S Ferris Douglass K |
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Affiliation: | Laboratory of Cancer Prevention, NCI at Frederick, Frederick, MD, USA; Nanobiology Program, CCR, NCI at Frederick, Frederick, MD, USA. yfeng@mail.ncifcrf.gov |
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Abstract: | Polo-like kinase functions are essential for the establishment of a normal bipolar mitotic spindle, although precisely how Plk1 regulates the spindle is uncertain. In this study, we report that the small GTP/GDP-binding protein Ran is associated with Plk1. Plk1 is capable of phosphorylating co-immunoprecipitated Ran in vitro on serine-135 and Ran is phosphorylated in vivo at the same site during mitosis when Plk1 is normally activated. Cell cultures over-expressing a Ran S135D mutant have significantly higher numbers of abnormal mitotic cells than those over-expressing either wild-type or S135A Ran. The abnormalities in S135D mutant cells are similar to cells over-expressing Plk1. Our data suggests that Ran is a physiological substrate of Plk1 and that Plk1 regulates the spindle organization partially through its phosphorylation on Ran. |
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Keywords: | Cytokinesis Mitosis GTP-binding proteins Plk1 Polo-like kinases Ran |
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