Cell Cycle-dependent Expression and Spindle Pole Localization of a Novel Human Protein Kinase, Aik, Related to Aurora of Drosophila and Yeast Ipl1

Abstract

Mutations in Aurora of Drosophila and related Saccharomyces cerevisiae Ipl1 kinase are known to cause abnormal chromosome segregation. We have 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 amino acid identities with the Aurora/Ipl1 protein kinase family; hence the cDNA is designated as aik(aurora/IPL1-related kinase). Amino acid sequence of C-terminal kinase domain of Aik shares 86, 86, 72, 59, and 49% identity with those of Xenopus XLP46APK and XLP46BPK, mouse STK-1, Aurora of Drosophila, and yeast Ipl1, respectively, whereas N-terminal domain of Aik shares high homology only with those of XLP46APK and XLP46BPK. Northern and Western blotting analyses revealed that Aik is expressed highly in testis and various proliferating cells including HeLa cells. In HeLa cells, the endogenous levels of aik mRNA and protein contents are tightly regulated during cell cycle progression. Both of these levels are low in G1/S, accumulate during G2/M, and reduce rapidly after mitosis. Its protein kinase activity is also enhanced at mitosis as inferred by exogenous casein phosphorylation. Immunofluorescence studies using a specific antibody have shown that Aik is localized to the spindle pole during mitosis, especially from prophase through anaphase. These results strongly suggest that Aik is a novel member of a protein kinase family possibly involved in a centrosome function(s) such as chromosome segregation or spindle formation. Mutations in Aurora of Drosophila and related Saccharomyces cerevisiae Ipl1 kinase are known to cause abnormal chromosome segregation. We have 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 amino acid identities with the Aurora/Ipl1 protein kinase family; hence the cDNA is designated as aik(aurora/IPL1-related kinase). Amino acid sequence of C-terminal kinase domain of Aik shares 86, 86, 72, 59, and 49% identity with those of Xenopus XLP46APK and XLP46BPK, mouse STK-1, Aurora of Drosophila, and yeast Ipl1, respectively, whereas N-terminal domain of Aik shares high homology only with those of XLP46APK and XLP46BPK. Northern and Western blotting analyses revealed that Aik is expressed highly in testis and various proliferating cells including HeLa cells. In HeLa cells, the endogenous levels of aik mRNA and protein contents are tightly regulated during cell cycle progression. Both of these levels are low in G1/S, accumulate during G2/M, and reduce rapidly after mitosis. Its protein kinase activity is also enhanced at mitosis as inferred by exogenous casein phosphorylation. Immunofluorescence studies using a specific antibody have shown that Aik is localized to the spindle pole during mitosis, especially from prophase through anaphase. These results strongly suggest that Aik is a novel member of a protein kinase family possibly involved in a centrosome function(s) such as chromosome segregation or spindle formation. Accurate segregation of chromosomes during mitosis is an important event in the progression of cell cycle. Chromosome segregation is a highly complex process requiring microtubule assembly and disassembly. Centrosome and pericentriolar materials play important roles in organizing the microtubules at interphase and mitotic phase. At the G1 phase of cell cycle, duplicated centrioles closely associate and function as a single unit, and then separate into two units at mitotic phase. Centrosome separation is initiated either before or after nuclear envelope breakdown, and then microtubules are arranged and the separated centrosome organizes a mitotic spindle. In accordance with chromosome movement toward the spindle pole, the spindle microtubules shorten. However, details of molecular mechanisms by which centrosomal cycle or microtubule nucleation is regulated have not been elucidated.Multiple lines of evidence suggest that protein phosphorylation plays a pivotal role in controlling spindle assembly and its functioning. Several centrosomal components are known to be phosphorylated inDrosophila (1Kellogg D.R. Oegema K. Raff J. Schneider K. Alberts B.M. Mol. Biol. Cell. 1995; 6: 1673-1684Google Scholar) and vertebrates (2Vandre D.D. Davis F.M. Rao P.N. Borisy G.G. Proc. Natl. Acad. Sci. U. S. A. 1984; 81: 4439-4443Google Scholar, 3Centonze V.E. Borisy G.G. J. Cell Sci. 1990; 95: 405-411Google Scholar, 4Verde F. Berrez J.M. Antony C. Karsenti E. J. Cell Biol. 1991; 112: 1177-1187Google Scholar, 5Kuriyama R. Maekawa T. Exp. Cell Res. 1992; 202: 345-354Google Scholar, 6Taagepera S. Campbell M.S. Gorbsky G.J. Exp. Cell Res. 1995; 221: 249-260Google Scholar). Phosphorylation of centrosomal proteins has been shown to control both the rate of the microtubule nucleation and its dynamic behavior (7Buendia B. Draetta G. Karsenti E. J. Cell Biol. 1992; 116: 1431-1442Google Scholar). The reversible phosphorylation may control the function of microtubule-based motor proteins such as a kinesin-like protein (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). Several genetic studies on fungi and fruit flies have identified various protein kinases and phosphatases that play intriguing roles in chromosome segregation (9Axton J.M. Dombradi V. Cohen P.T. Glover D.M. Cell. 1990; 63: 33-46Google Scholar, 10Chan C.S. Botstein D. Genetics. 1993; 135: 677-691Google Scholar, 11Glover D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar). In mammalian cells, centrosomal localization of several protein kinases has been reported on Cdc2 (12Bailly E. Doree M. Nurse P. Bornens M. EMBO J. 1989; 8: 3985-3995Google Scholar), Plk1 (13Golsteyn R.M. Mundt K.E. Fry A.M. Nigg E.A. J. Cell Biol. 1995; 129: 1617-1628Google Scholar), Fyn (14Ley S.C. Marsh M. Bebbington C.R. Proudfoot K. Jordan P. J. Cell Biol. 1994; 125: 639-649Google Scholar), Src (15David-Pfeuty T. Bagrodia S. Shalloway D. J. Cell Sci. 1993; 105: 613-628Google Scholar), and A kinase (16Nigg E.A. Schafer G. Hilz H. Eppenberger H.M. Cell. 1985; 41: 1039-1051Google Scholar).Among the protein kinases that have been implicated in the control of spindle function, the role of Cdc2/cyclin B complex is pivotal and has been well characterized (17Gallant P. Nigg E.A. J. Cell Biol. 1992; 117: 213-224Google Scholar). This kinase is activated during mitosis and inactivated immediately afterward. The Cdc2 kinase partly localized in the mitotic spindle is known to regulate the dynamics and length of microtubules (12Bailly E. Doree M. Nurse P. Bornens M. EMBO J. 1989; 8: 3985-3995Google Scholar). Ectopic of in HeLa cells cell with mitotic spindle (17Gallant P. Nigg E.A. J. Cell Biol. 1992; 117: 213-224Google Scholar). In a a kinesin-like motor protein identified as a Cdc2 which the centrosomal localization (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google kinases that control mitotic spindle have also been yeast K. A. Mol. Cell. Biol. 1993; Scholar), yeast H. Glover D.M. 1995; S. A. A. C. C. Glover D.M. 1991; Scholar), mammalian kinase (13Golsteyn R.M. Mundt K.E. Fry A.M. Nigg E.A. J. Cell Biol. 1995; 129: 1617-1628Google Proc. Natl. Acad. Sci. U. S. A. 1993; Scholar, R.M. J. A. T. Nigg E.A. J. Cell Sci. 1994; Scholar, Mol. Cell. Biol. 1993; Scholar, R. S. Cell 1994; Scholar, U. G. A. T. B. H. K. Proc. Natl. Acad. Sci. U. S. A. 1994; Scholar, R. Mol. Cell. Biol. 1995; Scholar), and Xenopus A. Scholar). The abnormal of spindle or separated spindle in which pole is Plk1 kinase is and activated at phase and at the of mitosis. The localization of the Plk1 protein is in both centrosome and mitotic spindle at phase. Plk1 is phosphorylated and activated by Cdc2 kinase R. P.M. S. K. J. Biol. 1995; Scholar). of the of Plk1 identified as kinesin-like and that Plk1 is a of the motor protein R. Mol. Cell. Biol. 1995; C.S. Mol. Cell. Biol. 1994; Scholar) and Aurora D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar) have kinase which are highly to and are to be involved in chromosome segregation. from closely at mitotic of function to a of the to separate and a spindle D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar). chromosomes at C.S. Botstein D. Genetics. 1993; 135: 677-691Google Scholar). The and the of these kinases have not been protein shown to in to Ipl1 protein kinase in yeast C.S. Mol. Cell. Biol. 1994; Scholar). of Aurora/Ipl1 family kinases have been isolated from or mouse H. K. T. K. Scholar), the of these proteins have not been well have a cDNA encoding a human novel which has a high homology with Aurora/Ipl1 family protein and at phase as well as spindle pole localization of Aik kinase suggest a role of the protein in centrosome have identified a novel human encoding a kinase designated as The Aik amino acid sequence of the amino acids in kinases and is closely related to of the Aurora/Ipl1 family protein which are known to be chromosome segregation in Drosophila D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar) and yeast C.S. Mol. Cell. Biol. 1994; Scholar). of cause chromosome C.S. Botstein D. Genetics. 1993; 135: 677-691Google Scholar). spindle and the chromosomes D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar). The of amino acid through Aik and two kinases in that closely related kinases to Aik in The sequence homology strongly that Aik is a member of the Aurora/Ipl1 family protein kinases from yeast to human and that play a role in chromosome segregation as Aurora and of aik by Northern blotting that high in testis and in and of Aik at protein levels in cell lines by Western blotting of the proliferating cells expressed Aik protein with HeLa cells the A of protein sequence revealed the of Aik in several such as or These results the of Aik in proliferating cells, its in cell The of mouse is high in the proliferating of and H. K. T. K. Scholar). The of the Aik and may suggest the of and are in chromosome is that the kinase Aik may also function at phase. The evidence Aik is expressed in a of proliferating or cells. Cell of Aik in HeLa cells by Northern and Western The levels of both are low in high in the of Aik after mitosis, a sequence to the on a Several in the Aik kinase amino acids amino acids and amino acids or of these function as a of Aik to be after kinase activity of Aik also at phase activity to be with the protein is that is at partly regulated by the in protein These results suggest that Aik plays a role in cell cycle at phase in to the function of the pole the N-terminal of Aik has homology with Ipl1, or STK-1, also be that the N-terminal to regulate the kinase is localized to centrosome and spindle pole from prophase to This localization as well as the during cell cycle that Aik has a in centrosome or spindle at phase. the localization of Aurora and Ipl1 has not been well the of these suggest that the localization of these proteins may also be at centrosome or spindle pole and may be involved in spindle the localization of Aik that may function in spindle localized protein kinases have been identified in cells, including Cdc2 (12Bailly E. Doree M. Nurse P. Bornens M. EMBO J. 1989; 8: 3985-3995Google Scholar), Plk1 (13Golsteyn R.M. Mundt K.E. Fry A.M. Nigg E.A. J. Cell Biol. 1995; 129: 1617-1628Google Scholar), Fyn (14Ley S.C. Marsh M. Bebbington C.R. Proudfoot K. Jordan P. J. Cell Biol. 1994; 125: 639-649Google Scholar), Src (15David-Pfeuty T. Bagrodia S. Shalloway D. J. Cell Sci. 1993; 105: 613-628Google Scholar), and A kinase (16Nigg E.A. Schafer G. Hilz H. Eppenberger H.M. Cell. 1985; 41: 1039-1051Google Scholar). of the kinases to function as of microtubule and spindle formation. Ectopic of in HeLa cells cell with mitotic spindle (17Gallant P. Nigg E.A. J. Cell Biol. 1992; 117: 213-224Google Scholar). In a of the of Cdc2 kinase identified to be a kinesin-like motor protein and to regulate the centrosomal localization (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). Plk1 is phosphorylated and activated by Cdc2 kinase R. P.M. S. K. J. Biol. 1995; Scholar). Aik phosphorylated in phase not that the protein kinase Aik may play a in centrosomal to Aik is a of Aik to Saccharomyces cerevisiae Aik to the not the sequence homology and the localization of Aik that these two kinases have not the is that of the in amino acid sequence Aik and Ipl1, a or a protein with Aik in yeast cells. human of yeast proteins are known to the to the yeast that the that Aik is not a human of to be Aik plays the role as Ipl1 in Aik has protein kinase the the is Several centrosomal components have been shown to be phosphorylated and to control the rate of microtubule dynamic behavior at the phosphorylation the function of a microtubule-based motor protein such as kinesin-like protein (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). The of Aik has not been has that Aurora or a high molecular phosphorylated in the in kinase that a Aik and phosphorylated with the The protein only from cells not The of Aik kinase may be a protein that in centrosome are the of Aik kinase and to the function of the Accurate segregation of chromosomes during mitosis is an important event in the progression of cell cycle. Chromosome segregation is a highly complex process requiring microtubule assembly and disassembly. Centrosome and pericentriolar materials play important roles in organizing the microtubules at interphase and mitotic phase. At the G1 phase of cell cycle, duplicated centrioles closely associate and function as a single unit, and then separate into two units at mitotic phase. Centrosome separation is initiated either before or after nuclear envelope breakdown, and then microtubules are arranged and the separated centrosome organizes a mitotic spindle. In accordance with chromosome movement toward the spindle pole, the spindle microtubules shorten. However, details of molecular mechanisms by which centrosomal cycle or microtubule nucleation is regulated have not been lines of evidence suggest that protein phosphorylation plays a pivotal role in controlling spindle assembly and its functioning. Several centrosomal components are known to be phosphorylated inDrosophila (1Kellogg D.R. Oegema K. Raff J. Schneider K. Alberts B.M. Mol. Biol. Cell. 1995; 6: 1673-1684Google Scholar) and vertebrates (2Vandre D.D. Davis F.M. Rao P.N. Borisy G.G. Proc. Natl. Acad. Sci. U. S. A. 1984; 81: 4439-4443Google Scholar, 3Centonze V.E. Borisy G.G. J. Cell Sci. 1990; 95: 405-411Google Scholar, 4Verde F. Berrez J.M. Antony C. Karsenti E. J. Cell Biol. 1991; 112: 1177-1187Google Scholar, 5Kuriyama R. Maekawa T. Exp. Cell Res. 1992; 202: 345-354Google Scholar, 6Taagepera S. Campbell M.S. Gorbsky G.J. Exp. Cell Res. 1995; 221: 249-260Google Scholar). Phosphorylation of centrosomal proteins has been shown to control both the rate of the microtubule nucleation and its dynamic behavior (7Buendia B. Draetta G. Karsenti E. J. Cell Biol. 1992; 116: 1431-1442Google Scholar). The reversible phosphorylation may control the function of microtubule-based motor proteins such as a kinesin-like protein (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). Several genetic studies on fungi and fruit flies have identified various protein kinases and phosphatases that play intriguing roles in chromosome segregation (9Axton J.M. Dombradi V. Cohen P.T. Glover D.M. Cell. 1990; 63: 33-46Google Scholar, 10Chan C.S. Botstein D. Genetics. 1993; 135: 677-691Google Scholar, 11Glover D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar). In mammalian cells, centrosomal localization of several protein kinases has been reported on Cdc2 (12Bailly E. Doree M. Nurse P. Bornens M. EMBO J. 1989; 8: 3985-3995Google Scholar), Plk1 (13Golsteyn R.M. Mundt K.E. Fry A.M. Nigg E.A. J. Cell Biol. 1995; 129: 1617-1628Google Scholar), Fyn (14Ley S.C. Marsh M. Bebbington C.R. Proudfoot K. Jordan P. J. Cell Biol. 1994; 125: 639-649Google Scholar), Src (15David-Pfeuty T. Bagrodia S. Shalloway D. J. Cell Sci. 1993; 105: 613-628Google Scholar), and A kinase (16Nigg E.A. Schafer G. Hilz H. Eppenberger H.M. Cell. 1985; 41: 1039-1051Google Scholar). the protein kinases that have been implicated in the control of spindle function, the role of Cdc2/cyclin B complex is pivotal and has been well characterized (17Gallant P. Nigg E.A. J. Cell Biol. 1992; 117: 213-224Google Scholar). This kinase is activated during mitosis and inactivated immediately afterward. The Cdc2 kinase partly localized in the mitotic spindle is known to regulate the dynamics and length of microtubules (12Bailly E. Doree M. Nurse P. Bornens M. EMBO J. 1989; 8: 3985-3995Google Scholar). Ectopic of in HeLa cells cell with mitotic spindle (17Gallant P. Nigg E.A. J. Cell Biol. 1992; 117: 213-224Google Scholar). In a a kinesin-like motor protein identified as a Cdc2 which the centrosomal localization (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). kinases that control mitotic spindle have also been yeast K. A. Mol. Cell. Biol. 1993; Scholar), yeast H. Glover D.M. 1995; S. A. A. C. C. Glover D.M. 1991; Scholar), mammalian kinase (13Golsteyn R.M. Mundt K.E. Fry A.M. Nigg E.A. J. Cell Biol. 1995; 129: 1617-1628Google Proc. Natl. Acad. Sci. U. S. A. 1993; Scholar, R.M. J. A. T. Nigg E.A. J. Cell Sci. 1994; Scholar, Mol. Cell. Biol. 1993; Scholar, R. S. Cell 1994; Scholar, U. G. A. T. B. H. K. Proc. Natl. Acad. Sci. U. S. A. 1994; Scholar, R. Mol. Cell. Biol. 1995; Scholar), and Xenopus A. Scholar). The abnormal of spindle or separated spindle in which pole is Plk1 kinase is and activated at phase and at the of mitosis. The localization of the Plk1 protein is in both centrosome and mitotic spindle at phase. Plk1 is phosphorylated and activated by Cdc2 kinase R. P.M. S. K. J. Biol. 1995; Scholar). of the of Plk1 identified as kinesin-like and that Plk1 is a of the motor protein R. Mol. Cell. Biol. 1995; Scholar). Ipl1 C.S. Mol. Cell. Biol. 1994; Scholar) and Aurora D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar) have kinase which are highly to and are to be involved in chromosome segregation. from closely at mitotic of function to a of the to separate and a spindle D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar). chromosomes at C.S. Botstein D. Genetics. 1993; 135: 677-691Google Scholar). The and the of these kinases have not been protein shown to in to Ipl1 protein kinase in yeast C.S. Mol. Cell. Biol. 1994; Scholar). of Aurora/Ipl1 family kinases have been isolated from or mouse H. K. T. K. Scholar), the of these proteins have not been well We have a cDNA encoding a human novel which has a high homology with Aurora/Ipl1 family protein and at phase as well as spindle pole localization of Aik kinase suggest a role of the protein in centrosome have identified a novel human encoding a kinase designated as The Aik amino acid sequence of the amino acids in kinases and is closely related to of the Aurora/Ipl1 family protein which are known to be chromosome segregation in Drosophila D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar) and yeast C.S. Mol. Cell. Biol. 1994; Scholar). of cause chromosome C.S. Botstein D. Genetics. 1993; 135: 677-691Google Scholar). spindle and the chromosomes D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar). The of amino acid through Aik and two kinases in that closely related kinases to Aik in The sequence homology strongly that Aik is a member of the Aurora/Ipl1 family protein kinases from yeast to human and that play a role in chromosome segregation as Aurora and of aik by Northern blotting that high in testis and in and of Aik at protein levels in cell lines by Western blotting of the proliferating cells expressed Aik protein with HeLa cells the A of protein sequence revealed the of Aik in several such as or These results the of Aik in proliferating cells, its in cell The of mouse is high in the proliferating of and H. K. T. K. Scholar). The of the Aik and may suggest the of and are in chromosome is that the kinase Aik may also function at phase. The evidence Aik is expressed in a of proliferating or cells. Cell of Aik in HeLa cells by Northern and Western The levels of both are low in high in the of Aik after mitosis, a sequence to the on a Several in the Aik kinase amino acids amino acids and amino acids or of these function as a of Aik to be after kinase activity of Aik also at phase activity to be with the protein is that is at partly regulated by the in protein These results suggest that Aik plays a role in cell cycle at phase in to the function of the pole the N-terminal of Aik has homology with Ipl1, or STK-1, also be that the N-terminal to regulate the kinase is localized to centrosome and spindle pole from prophase to This localization as well as the during cell cycle that Aik has a in centrosome or spindle at phase. the localization of Aurora and Ipl1 has not been well the of these suggest that the localization of these proteins may also be at centrosome or spindle pole and may be involved in spindle the localization of Aik that may function in spindle localized protein kinases have been identified in cells, including Cdc2 (12Bailly E. Doree M. Nurse P. Bornens M. EMBO J. 1989; 8: 3985-3995Google Scholar), Plk1 (13Golsteyn R.M. Mundt K.E. Fry A.M. Nigg E.A. J. Cell Biol. 1995; 129: 1617-1628Google Scholar), Fyn (14Ley S.C. Marsh M. Bebbington C.R. Proudfoot K. Jordan P. J. Cell Biol. 1994; 125: 639-649Google Scholar), Src (15David-Pfeuty T. Bagrodia S. Shalloway D. J. Cell Sci. 1993; 105: 613-628Google Scholar), and A kinase (16Nigg E.A. Schafer G. Hilz H. Eppenberger H.M. Cell. 1985; 41: 1039-1051Google Scholar). of the kinases to function as of microtubule and spindle formation. Ectopic of in HeLa cells cell with mitotic spindle (17Gallant P. Nigg E.A. J. Cell Biol. 1992; 117: 213-224Google Scholar). In a of the of Cdc2 kinase identified to be a kinesin-like motor protein and to regulate the centrosomal localization (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). Plk1 is phosphorylated and activated by Cdc2 kinase R. P.M. S. K. J. Biol. 1995; Scholar). Aik phosphorylated in phase not that the protein kinase Aik may play a in centrosomal to Aik is a of Aik to Saccharomyces cerevisiae Aik to the not the sequence homology and the localization of Aik that these two kinases have not the is that of the in amino acid sequence Aik and Ipl1, a or a protein with Aik in yeast cells. human of yeast proteins are known to the to the yeast that the that Aik is not a human of to be Aik plays the role as Ipl1 in Aik has protein kinase the the is Several centrosomal components have been shown to be phosphorylated and to control the rate of microtubule dynamic behavior at the phosphorylation the function of a microtubule-based motor protein such as kinesin-like protein (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). The of Aik has not been has that Aurora or a high molecular phosphorylated in the in kinase that a Aik and phosphorylated with the The protein only from cells not The of Aik kinase may be a protein that in centrosome are the of Aik kinase and to the function of the We have identified a novel human encoding a kinase designated as The Aik amino acid sequence of the amino acids in kinases and is closely related to of the Aurora/Ipl1 family protein which are known to be chromosome segregation in Drosophila D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar) and yeast C.S. Mol. Cell. Biol. 1994; Scholar). of cause chromosome C.S. Botstein D. Genetics. 1993; 135: 677-691Google Scholar). spindle and the chromosomes D.M. Leibowitz M.H. McLean D.A. Parry H. Cell. 1995; 81: 95-105Google Scholar). The of amino acid through Aik and two kinases in that closely related kinases to Aik in The sequence homology strongly that Aik is a member of the Aurora/Ipl1 family protein kinases from yeast to human and that play a role in chromosome segregation as Aurora and The of aik by Northern blotting that high in testis and in and of Aik at protein levels in cell lines by Western blotting of the proliferating cells expressed Aik protein with HeLa cells the A of protein sequence revealed the of Aik in several such as or These results the of Aik in proliferating cells, its in cell The of mouse is high in the proliferating of and H. K. T. K. Scholar). The of the Aik and may suggest the of and are in chromosome is that the kinase Aik may also function at phase. The evidence Aik is expressed in a of proliferating or cells. Cell of Aik in HeLa cells by Northern and Western The levels of both are low in high in the of Aik after mitosis, a sequence to the on a Several in the Aik kinase amino acids amino acids and amino acids or of these function as a of Aik to be after phase. The kinase activity of Aik also at phase activity to be with the protein is that is at partly regulated by the in protein These results suggest that Aik plays a role in cell cycle at phase in to the function of the pole the N-terminal of Aik has homology with Ipl1, or STK-1, also be that the N-terminal to regulate the kinase Aik is localized to centrosome and spindle pole from prophase to This localization as well as the during cell cycle that Aik has a in centrosome or spindle at phase. the localization of Aurora and Ipl1 has not been well the of these suggest that the localization of these proteins may also be at centrosome or spindle pole and may be involved in spindle the localization of Aik that may function in spindle localized protein kinases have been identified in cells, including Cdc2 (12Bailly E. Doree M. Nurse P. Bornens M. EMBO J. 1989; 8: 3985-3995Google Scholar), Plk1 (13Golsteyn R.M. Mundt K.E. Fry A.M. Nigg E.A. J. Cell Biol. 1995; 129: 1617-1628Google Scholar), Fyn (14Ley S.C. Marsh M. Bebbington C.R. Proudfoot K. Jordan P. J. Cell Biol. 1994; 125: 639-649Google Scholar), Src (15David-Pfeuty T. Bagrodia S. Shalloway D. J. Cell Sci. 1993; 105: 613-628Google Scholar), and A kinase (16Nigg E.A. Schafer G. Hilz H. Eppenberger H.M. Cell. 1985; 41: 1039-1051Google Scholar). of the kinases to function as of microtubule and spindle formation. Ectopic of in HeLa cells cell with mitotic spindle (17Gallant P. Nigg E.A. J. Cell Biol. 1992; 117: 213-224Google Scholar). In a of the of Cdc2 kinase identified to be a kinesin-like motor protein and to regulate the centrosomal localization (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). Plk1 is phosphorylated and activated by Cdc2 kinase R. P.M. S. K. J. Biol. 1995; Scholar). Aik phosphorylated in phase not that the protein kinase Aik may play a in centrosomal to Aik is a of Aik to Saccharomyces cerevisiae Aik to the not the sequence homology and the localization of Aik that these two kinases have not the is that of the in amino acid sequence Aik and Ipl1, a or a protein with Aik in yeast cells. human of yeast proteins are known to the to the yeast that the that Aik is not a human of to be Aik plays the role as Ipl1 in Aik has protein kinase the the is Several centrosomal components have been shown to be phosphorylated and to control the rate of microtubule dynamic behavior at the phosphorylation the function of a microtubule-based motor protein such as kinesin-like protein (8Blangy A. Lane H.A. d'Herin P.M. Kress M. Nigg E.A. Cell. 1995; 83: 1159-1169Google Scholar). The of Aik has not been has that Aurora or a high molecular phosphorylated in the in kinase that a Aik and phosphorylated with the The protein only from cells not The of Aik kinase may be a protein that in centrosome We are the of Aik kinase and to the function of the We are to M. cells, H. T. and C. S. of with results on We of to a and of in of specific We are to of