CELL CYCLE-DEPENDENT EXPRESSION AND SPINDLE POLE LOCALIZATION OF A NOVEL HUMAN PROTEIN-KINASE, AIK, RELATED TO AURORA OF DROSOPHILA AND YEAST IPL1

Mutations in Aurora of Drosophila and related Saccharomyces cerevisiae Ipl1 kinase are known to cause abnormal chromosome segregation. We ha ve isolated a cDNA encoding a novel human protein kinase of 402 amino acids with a predicted molecular mass of 45.9 kDa, which shares high a mino acid identities with the Aurora/Ipl1 protein kinase family; hence the cDNA is designated as Aik (aurora/IPL1-related kinase). Amino aci d sequence of C-terminal kinase domain of Aik shares 86, 86, 72, 59, a nd 49% identity with those of Xenopus XLP46APK and XLP46BPK, mouse STK -1, Aurora of Drosophila, and yeast Ipl1, respectively, whereas N-term inal domain of Aik shares high homology only with those of XLP46APK an d XLP46BPK, Northern and Western blotting analyses revealed that Aik i s expressed highly in testis and various proliferating cells including HeLa cells. In HeLa cells, the endogenous levels of aik mRNA and prot ein contents are tightly regulated during cell cycle progression. Both of these levels are low in G(1)/S, accumulate during G(2)/M, and redu ce rapidly after mitosis. Its protein kinase activity is also enhanced at mitosis as inferred by exogenous casein phosphorylation. Immunoflu orescence studies using a specific antibody have shown that Aik is loc alized to the spindle pole during mitosis, especially from prophase th rough anaphase. These results strongly suggest that Aik is a novel mem ber of a protein kinase family possibly involved in a centrosome funct ion(s) such as chromosome segregation or spindle formation.