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

Ming Ying Tsai, Christiane Wiese, Kan Cao, Ona Martin, Peter Donovan, Joan Ruderman, Claude Prigent, Yixian Zheng

Research output: Contribution to journalArticlepeer-review

316 Scopus citations

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-α and -β. 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-α and -β, 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.

Original languageEnglish (US)
Pages (from-to)242-248
Number of pages7
JournalNature cell biology
Volume5
Issue number3
DOIs
StatePublished - Mar 1 2003
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cell Biology

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