Determinants for Aurora-A activation and Aurora-B discrimination by TPX2.
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.
Bayliss
Richard
R
European Molecular Biology Laboratory, EMBL, Meyerhofstrasse 1, Heidelberg, Germany.
Sardon
Teresa
T
Ebert
Judith
J
Lindner
Doris
D
Vernos
Isabelle
I
Conti
Elena
E
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D020134:Catalytic Domain; D018797:Cell Cycle Proteins / Q000378:metabolism*; D004330:Drosophila; D004789:Enzyme Activation; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D008958:Models, Molecular; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D008941:Spindle Apparatus / Q000378:metabolism; D029867:Xenopus Proteins
D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010455:Peptides; D010750:Phosphoproteins; C122167:TPX2 protein, human; D029867:Xenopus Proteins; D005982:Glutathione Transferase; D011494:Protein Kinases; C112134:AURKA protein, Xenopus; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases