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© The Rockefeller University Press, 0021-9525/1997//643 $5.00
The Journal of Cell Biology, Volume 138, Number 3, , 1997 643-656

A Novel Mammalian, Mitotic Spindle–associated Kinase Is Related to Yeast and Fly Chromosome Segregation Regulators

Ganesan Gopalan^*, Clarence S.M. Chan, and Peter J. Donovan^*

^* Cell Biology of Development and Differentiation Group, ABL Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201; and Department of Microbiology, University of Texas, Austin, Texas 78712

We describe a novel mammalian protein kinase related to two newly identified yeast and fly kinases—Ipl1 and aurora, respectively—mutations in which cause disruption of chromosome segregation. We have designated this kinase as Ipl1- and aurora-related kinase 1 (IAK1). IAK1 expression in mouse fibroblasts is tightly regulated temporally and spatially during the cell cycle. Transcripts first appear at G₁/S boundary, are elevated at M-phase, and disappear rapidly after completion of mitosis. The protein levels and kinase activity of IAK1 are also cell cycle regulated with a peak at M-phase. IAK1 protein has a distinct subcellular and temporal pattern of localization. It is first identified on the centrosomes immediately after the duplicated centrosomes have separated. The protein remains on the centrosome and the centrosome-proximal part of the spindle throughout mitosis and is detected weakly on midbody microtubules at telophase and cytokinesis. In cells recovering from nocodazole treatment and in taxol-treated mitotic cells, IAK1 is associated with microtubule organizing centers. A wild-type and a mutant form of IAK1 cause mitotic spindle defects and lethality in ipl1 mutant yeast cells but not in wild-type cells, suggesting that IAK1 interferes with Ipl1p function in yeast. Taken together, these data strongly suggest that IAK1 may have an important role in centrosome and/ or spindle function during chromosome segregation in mammalian cells. We suggest that IAK1 is a new member of an emerging subfamily of the serine/threonine kinase superfamily. The members of this subfamily may be important regulators of chromosome segregation.

Abbreviations used in this paper: GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IAK1, Ipl1- and aurora-related kinase 1; MBP, myelin basic protein; MPF, M-phase promoting factor; MTOC, microtubule organizing center; PKA, protein kinase A; Plk1, Polo-like kinase; ts, temperature-sensitive; T/STK, testis-derived serine/threonine kinases.

This research was sponsored in part by the Department of Health and Human Services under contract with Advanced Bioscience Laboratories (P.J. Donovan), and the National Institutes of Health (GM45185) and the Council for Tobacco Research (#4496) (C.S.M. Chan).

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