Cell Cycle-dependent Expression and Centrosome Localization of a Third Human Aurora/Ipl1-related Protein Kinase, AIK3

Masashi Kimura,Yoichi Matsuda,Takashi Yoshioka,Yukio Okano

doi:10.1074/jbc.274.11.7334

Masashi Kimura, Yoichi Matsuda + Show 2 more

Open Access

https://doi.org/10.1074/jbc.274.11.7334

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Abstract

We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. In the present study, a third human cDNA (AIK3) highly homologous to aurora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA encodes 309 amino acids with a predicted molecular mass of 35.9 kDa. C-terminal kinase domain of AIK3 protein shares high amino acid sequence identities with those of Aurora/Ipl1 family protein kinases including human AIK, human AIK2, Xenopus pEg2, Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of AIK3 protein shares little homology with any other Aurora/Ipl1 family members. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Northern blot analyses revealed that AIK3 expression was limited to testis. The expression levels of AIK3 in several cancer cell lines were elevated severalfold compared with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein level is low in G1/S, accumulates during G2/M, and reduces after mitosis. Immunofluorescence studies using a specific antibody have shown that AIK3 is localized to centrosome during mitosis from anaphase to cytokinesis. These results suggest that AIK3 may play a role(s) in centrosome function at later stages of mitosis.

Highlights

We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation
Recent investigations revealed the presence of members of Aurora/Ipl1 family kinases in vertebrates, such as human AIK/BTAK [13, 14], human AIK2 [15, 16], mouse STK-1 [17], mouse AYK1/IAK1 [18, 19], rat AIM-1 [20], or Xenopus pEg2 [21], but the functions of these proteins have not been studied well
AIK gene was mapped to human chromosome 20q13.2–13.3 [14, 22], and IAK1 gene was mapped to the distal region of mouse chromosome 2 [23]

Summary

Introduction

We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Human AIK2, rat AIM-1, and mouse STK-1 have high amino acid sequence identities with each other along their full length, and these three proteins constitute the second subfamily of the Aurora/Ipl1 protein kinase family.

Results

Conclusion