Functional implication of human serine/threonine kinase, hAIK, 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 identified a serine/threonine kinase, hAIK, from human hepatic cells using degenerated polymerase chain reactions with a pair of primers derived from the highly conserved sequence in the catalytic domain of kinases. The full-length hAIK cDNA was then obtained, which contained 403 amino acids and was homologous to Drosophila Aurora2 and yeast Ipl1 proteins. Northern blotting analysis 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 activity 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, overexpression of hAIK in cancer cell lines (HEK293T and HeLa) appeared to inhibit cell cycle progression. None of these phenomena were observed in hAIKm whose kinase activity was rendered inactive. Our results suggest that hAIK protein/activity might modulate cell cycle progression by interacting with the centrosomes and/or proteins associated with these structures.
Yang
S C
SC
Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan, ROC.
Huang
C H
CH
Chen
N J
NJ
Chou
C K
CK
Lin
C H
CH
D000595:Amino Acid Sequence; D000818:Animals; D064127:Aurora Kinases; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics; D002453:Cell Cycle / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics; D008297:Male; D008938:Mitosis / Q000502:physiology; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000201:enzymology; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D011994:Recombinant Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases