Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B Kinase stimulates Aurora B kinase activity.
How the events of mitosis are coordinated is not well understood. Intriguing mitotic regulators include the chromosomal passenger proteins. Loss of either of the passengers inner centromere protein (INCENP) or the Aurora B kinase results in chromosome segregation defects and failures in cytokinesis. Furthermore, INCENP and Aurora B have identical localization patterns during mitosis and directly bind each other in vitro. These results led to the hypothesis that INCENP is a direct substrate of Aurora B. Here we show that the Caenorhabditis elegans Aurora B kinase AIR-2 specifically phosphorylated the C. elegans INCENP ICP-1 at two adjacent serines within the carboxyl terminus. Furthermore, the full length and a carboxyl-terminal fragment of ICP-1 stimulated AIR-2 kinase activity. This increase in AIR-2 activity required that AIR-2 phosphorylate ICP-1 because mutation of both serines in the AIR-2 phosphorylation site of ICP-1 abolished the potentiation of AIR-2 kinase activity by ICP-1. Thus, ICP-1 is directly phosphorylated by AIR-2 and functions in a positive feedback loop that regulates AIR-2 kinase activity. Since the Aurora B phosphorylation site within INCENP and the functions of INCENP and Aurora B have been conserved among eukaryotes, the feedback loop we have identified is also likely to be evolutionarily conserved.
Bishop
John D
JD
Department of Molecular Genetics, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Schumacher
Jill M
JM
D000595:Amino Acid Sequence; D000818:Animals; D064127:Aurora Kinases; D017173:Caenorhabditis elegans / Q000201:enzymology; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins / Q000378:metabolism; D008938:Mitosis; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D002868:Chromosomal Proteins, Non-Histone; D003598:Cytoskeletal Proteins; D011993:Recombinant Fusion Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases