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A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly.

Abstract : The activated form of Ran (Ran-GTP) stimulates spindle assembly in Xenopus laevis egg extracts, presumably by releasing spindle assembly factors, such as TPX2 (target protein for Xenopus kinesin-like protein 2) and NuMA (nuclear-mitotic apparatus protein) from the inhibitory binding of importin-alpha and -beta. We report here that Ran-GTP stimulates the interaction between TPX2 and the Xenopus Aurora A kinase, Eg2. This interaction causes TPX2 to stimulate both the phosphorylation and the kinase activity of Eg2 in a microtubule-dependent manner. We show that TPX2 and microtubules promote phosphorylation of Eg2 by preventing phosphatase I (PPI)-induced dephosphorylation. Activation of Eg2 by TPX2 and microtubules is inhibited by importin-alpha and -beta, although this inhibition is overcome by Ran-GTP both in the egg extracts and in vitro with purified proteins. As the phosphorylation of Eg2 stimulated by the Ran-GTP-TPX2 pathway is essential for spindle assembly, we hypothesize that the Ran-GTP gradient established by the condensed chromosomes is translated into the Aurora A kinase gradient on the microtubules to regulate spindle assembly and dynamics.
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https://www.hal.inserm.fr/inserm-00966479
Contributor : Claude Prigent <>
Submitted on : Wednesday, March 26, 2014 - 4:39:56 PM
Last modification on : Thursday, April 4, 2019 - 11:30:04 AM

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Ming-Ying Tsai, Christiane Wiese, Kan Cao, Ona Martin, Peter Donovan, et al.. A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly.. Nature Cell Biology, Nature Publishing Group, 2003, 5 (3), pp.242-8. ⟨10.1038/ncb936⟩. ⟨inserm-00966479⟩

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