Determinants for Aurora-A Activation and Aurora-B Discrimination by TPX2

 Abstract

The mitotic kinases Aurora-A and Aurora-B have similar amino-acid sequences but are differently localised and regulated during cell division. The basis for their interactions with different and specific regulators is unclear. Surprisingly, our recent structural studies indicate that TPX2 regulates Aurora-A activity by binding at a site that is conserved almost completely on Aurora-B. Here we investigate molecular determinants of TPX2-Aurora-A recognition. Using structure-based mutagenesis, we show that a single amino-acid difference on the surface of the kinase catalytic domain is key to the precision with which TPX2 discriminates between Aurora-A and Aurora-B. The conservation at this amino-acid position suggests that this discriminatory mechanism is likely to be conserved in higher eukaryotes.

Full Text Options
Article
Metrics
 Share
 Full Text
 Info
Pages
402 - 405
doi
10.4161/cc.3.4.777
Type
Extra Views
 Metrics
 Cite This Article
 Permissions
 Permissions
 Reprints
Determinants for Aurora-A Activation and Aurora-B Discrimination by TPX2