title: 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.
authors.affiliation: Department of Embryology, Carnegie Institution of Washington/Howard Hughes Medical Institute, Baltimore, MD 21210, USA.
authors.forename: Ming-Ying
authors.initials: MY
authors.lastname: Tsai
authors.forename: Christiane
authors.initials: C
authors.lastname: Wiese
authors.forename: Kan
authors.initials: K
authors.lastname: Cao
authors.forename: Ona
authors.initials: O
authors.lastname: Martin
authors.forename: Peter
authors.initials: P
authors.lastname: Donovan
authors.forename: Joan
authors.initials: J
authors.lastname: Ruderman
authors.forename: Claude
authors.initials: C
authors.lastname: Prigent
authors.forename: Yixian
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D064127:Aurora Kinases; D018797:Cell Cycle Proteins; D011494:Protein Kinases / Q000302:isolation & purification / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000201:enzymology*; D029867:Xenopus Proteins; D014982:Xenopus laevis; D020931:ran GTP-Binding Protein / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D011994:Recombinant Proteins; D029867:Xenopus Proteins; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D020931:ran GTP-Binding Protein