A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly.
Nat Cell Biol
; 5(3): 242-8, 2003 Mar.
Article
in En
| MEDLINE
| ID: mdl-12577065
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.
Search on Google
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Kinases
/
Signal Transduction
/
Ran GTP-Binding Protein
/
Spindle Apparatus
Limits:
Animals
Language:
En
Journal:
Nat Cell Biol
Year:
2003
Type:
Article
Affiliation country:
United States