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

Nat Cell Biol. 2003 Mar;5(3):242-8. doi: 10.1038/ncb936.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aurora Kinases
  • Cell Cycle Proteins
  • Protein Kinases / isolation & purification
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Signal Transduction*
  • Spindle Apparatus / enzymology*
  • Xenopus Proteins
  • Xenopus laevis
  • ran GTP-Binding Protein / isolation & purification
  • ran GTP-Binding Protein / metabolism*

Substances

  • Cell Cycle Proteins
  • Recombinant Proteins
  • Xenopus Proteins
  • Protein Kinases
  • AURKA protein, Xenopus
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • ran GTP-Binding Protein