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Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor

Abstract

A novel human protein kinase, designated kpm, was identified and molecularly cloned. The isolated cDNA clone had an open reading frame consisting of 1088 amino acid residues with a putative kinase domain located near the carboxy-terminus. Homology search revealed that kpm belongs to a subfamily of serine/threonine protein kinases including warts/lats, a Drosophila tumor suppressor. Among these, kpm is most homologous to, but distinct from, recently reported LATS1, a human homolog of Drosophila warts/lats. Northern blot analysis disclosed that kpm is expressed as a 6.0 kb transcript in most of the tissues examined and also as an additional shorter 4.0 kb transcript in testis. Western blotting using polyclonal rabbit anti-kpm antibody detected kpm protein as a band with an apparent Mr of 150 kD. Immune complex kinase assay of HA-tagged kpm showed that kpm had kinase activity and phosphorylated itself in vitro. Studies with synchronized HeLa cells indicated that kpm protein was expressed relatively constantly throughout the cell cycle and underwent significant phosphorylation at mitotic phase. These results suggest that kpm plays a role in cell cycle progression during mitosis and its deletion or dysfunction might be involved in certain types of human cancers.

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References

  • Hanks SK and Quinn AM. . 1991 Methods Enzymol 200: 38–62.

  • Heintz N, Sive HL and Roeder RG. . 1983 Mol. Cell. Biol. 3: 539–550.

  • Hunter T. . 1995 Cell 80: 225–236.

  • Imura A, Hori T, Imada K, Ishikawa T, Tanaka Y, Maeda M, Imamura S and Uchiyama T. . 1996 J. Exp. Med. 183: 2185–2195.

  • Johnston LH, Eberly SL, Chapman JW, Araki H and Sugino A. . 1990 Mol. Cell. Biol. 10: 1358–1366.

  • Justice RW, Zilian O, Woods DF, Noll M and Bryant PJ. . 1995 Gene Dev. 9: 534–546.

  • Koeffler HP, Billing R, Lusis AJ, Sparkes R and Golde DW. . 1980 Blood 56: 265–273.

  • Mahadevan MS, Amemiya C, Jansen G, Sabourin L, Baird S, Neville CE, Wormskamp N, Segers B, Batzer M, Lamerdin J, de Jong P, Wieringa B and Korneluk RG. . 1993 Hum. Mol. Genet. 2: 299–304.

  • Millward T, Cron P and Hemmings BA. . 1995 Proc. Natl. Acad. Sci. USA 92: 5022–5026.

  • Millward T, Heinzmann CW, Schäfer BW and Hemmings BA. . 1998 EMBO J. 17: 5913–5922.

  • Morgan DO. . 1997 Annu. Rev. Cell. Dev. Biol. 13: 261–291.

  • Nishiyama Y, Hirota T, Morisaki T, Hara T, Marumoto T, Iida S, Makino K, Yamamoto H, Hiraoka T, Kitamura N and Saya H. . 1999 FEBS Lett. 459: 159–165.

  • Nurse P. . 1994 Cell 79: 547–550.

  • St John MAR, Tao W, Fei X, Fukumoto R, Carcangiu ML, Brownstein DG, Parlow AF, McGrath J and Xu T. . 1998 Nature Genet 21: 182–186.

  • Tao W, Zhang S, Turenchalk GS, Stewart RA, St John MAR, Chen W and Xu T. . 1998 Nature Genet 21: 177–181.

  • Toyn J, Araki H, Sugino A and Johnston LH. . 1991 Gene 104: 63–70.

  • Vallejo AN, Pogulis RJ and Pease LR. . 1995 In PCR Primer: A Laboratory Manual, eds. Dieffenbach CW and Dveksler GS. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.

  • Verde F, Wiley DJ and Nurse P. . 1998 Proc. Natl. Acad. Sci. USA 95: 7526–7531.

  • Watanabe N, Broome M and Hunter T. . 1995 EMBO J. 14: 1878–1891.

  • Xu T, Wang W, Zhang S, Stewart RA and Yu W. . 1995 Development 121: 1053–1063.

  • Yarden O, Plamann M, Ebbole DJ and Yanofsky C. . 1992 EMBO J. 11: 2159–2166.

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Acknowledgements

We thank Dr K Maruyama (Tokyo Medical and Dental University) for providing pME18S expression vector and Ms K Fukunaga for excellent technical assistance. This work was partly supported by grants-in-aid from the Ministry of Education, Science and Culture of Japan.

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Hori, T., Takaori-Kondo, A., Kamikubo, Y. et al. Molecular cloning of a novel human protein kinase, kpm, that is homologous to warts/lats, a Drosophila tumor suppressor. Oncogene 19, 3101–3109 (2000). https://doi.org/10.1038/sj.onc.1203659

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