Functional implication of human serine/threonine kinase, hAlK, in cell cycle progression

Protein phosphorylation is involved in many biological activities and plays important roles in cell cycle progression. In the present study, we identi fied a serine/threonine kinase, hAIK, from human hepatic cells using degene rated polymerase chain reactions with a pair of primers derived from the hi ghly conserved sequence in the catalytic domain of kinases, The full-length hAIK cDNA was then obtained, which contained 403 amino acids and was homol ogous to Drosophila Aurora2 and yeast Ipl1 proteins. Northern blotting anal ysis revealed that hAIK was highly expressed in the testis but not in other tissues. Expressions of hAIK drastically increased in cancer tissues/cell lines but not in fibroblasts or nontumorigenic cell lines. The recombinant hAIK protein phosphorylated itself and histone H1; this phosphorylation act ivity was totally abolished after a point mutation at the catalytic domain (hAIKm), During the interphase cell, hAIK was found mainly in the cytoplasm ; during mitosis hAIK accumulated at the centrosomes. In addition, overexpr ession of hAIK in cancer cell lines (HEK293T and HeLa) appeared to inhibit cell cycle progression. None of these phenomena were observed in hAIKm whos e kinase activity was rendered inactive. Our results suggest that hAIK prot ein/activity might modulate cell cycle progression by interacting with the centrosomes and/or proteins associated with these structures. Copyright (C) 2000 National Science Council. ROC and S. Karger AG. Basel.