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Cdk2 associates with MAP Kinase in vivo and its nuclear translocation is dependent on MAP Kinase activation in IL-2-dependent Kit 225 T lymphocytes

Abstract

Cell proliferation is controlled by cdk2 which in association with cyclin E and A regulates G1/S transition and S phase progression. cdk2 activation is dependent on its localization in the nucleus where regulatory mediators are found. We report that activation of cdk2 is associated with the formation of cdk2/MAP Kinase complexes. cdk2 associates with both inactive and activated MAP Kinase. Prevention of MAP Kinase activation by the MEK inhibitor PD98059 inhibits both activation and nuclear localization of cdk2 and S phase entry. These findings indicate that the nuclear translocation of cdk2 is associated with the formation of molecular complexes containing active MAP Kinase and is dependent on MAP Kinase activation.

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References

  • Alessandrini A, Crews CM and Erikson RL. . 1992 Proc. Natl. Acad. Sci. USA 89: 8200–8204.

  • Alessi DR, Cuenda A, Cohen P, Dudley DT and Saltiel AR. . 1995 J. Biol. Chem. 270: 27489–27494.

  • Anderson NG, Maller JL, Tonks NK and Sturgill TW. . 1990 Nature 343: 651–653.

  • Bresnahan WA, Boldogh I, Ma T, Albrecht T and Thompson EA. . 1996 Cell Growth Differ. 7: 1283–1290.

  • Brunet A, Roux D, Lenormand P, Dowd S, Keyse S and Pouyssegur J. . 1999 EMBO J. 18: 664–674.

  • Cowley S, Paterson H, Kemp P and Marshall CJ. . 1994 Cell 77: 841–852.

  • Crews CM, Alessandrini A and Erikson RL. . 1992 Science 258: 478–480.

  • Diehl JA and Sherr CJ. . 1997 Mol. Cell Biol. 17: 7362–7374.

  • Dudley DT, Pang L, Decker SJ, Bridges AJ and Saltiel AR. . 1995 Proc. Natl. Acad. Sci. USA 92: 7686–7689.

  • Dulic V, Lees E and Reed SI. . 1992 Science 257: 1958–1961.

  • el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW and Vogelstein B. . 1993 Cell 75: 817–825.

  • Ettehadieh E, Sanghera JS, Pelech SL, Hess-Bienz D, Watts J, Shastri N and Aebersold R. . 1992 Science 255: 853–855.

  • Fisher RP. . 1997 Curr. Opin. Genet. Dev. 7: 32–38.

  • Fotedar A, Cannella D, Fitzgerald P, Rousselle T, Gupta S, Doree M and Fotedar R. . 1996 J. Biol. Chem. 271: 31627–31637.

  • Fukuda M, Gotoh I, Gotoh Y and Nishida E. . 1996 J. Biol. Chem. 271: 20024–20028.

  • Gille H, Sharrocks AD and Shaw PE. . 1992 Nature 358: 414–417.

  • Gorlich D and Mattaj IW. . 1996 Science 271: 1513–1518.

  • Gu Y, Rosenblatt J and Morgan DO. . 1992 EMBO J. 11: 3995–4005.

  • Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ. . 1993 Cell 75: 805–816.

  • Hoffmann I, Draetta G and Karsenti E. . 1994 EMBO J. 13: 4302–4310.

  • Honda R, Ohba Y, Nagata A, Okayama H and Yasuda H. . 1993 FEBS Lett. 318: 331–334.

  • Hori T, Uchiyama T, Tsudo M, Umadome H, Ohno H, Fukuhara S, Kita K and Uchino H. . 1987 Blood 70: 1069–1072.

  • Janknecht R, Ernst WH, Pingoud V and Nordheim A. . 1993 EMBO J. 12: 5097–5104.

  • Jinno S, Suto K, Nagata A, Igarashi M, Kanaoka Y, Nojima H and Okayama H. . 1994 EMBO J. 13: 1549–1556.

  • Khokhlatchev AV, Canagarajah B, Wilsbacher J, Robinson M, Atkinson M, Goldsmith E and Cobb MH. . 1998 Cell 93: 605–615.

  • LaBaer J, Garrett MD, Stevenson LF, Slingerland JM, Sandhu C, Chou HS, Fattaey A and Harlow E. . 1997 Genes Dev. 11: 847–862.

  • Labbe JC, Martinez AM, Fesquet D, Capony JP, Darbon JM, Derancourt J, Devault A, Morin N, Cavadore JC and Doree M. . 1994 EMBO J. 13: 5155–5164.

  • Leevers SJ and Marshall CJ. . 1992 EMBO J. 11: 569–574.

  • Lenormand P, Sardet C, Pages G, L'Allemain G, Brunet A and Pouyssegur J. . 1993 J. Cell Biol. 122: 1079–1088.

  • Lew DJ and Kornbluth S. . 1996 Curr. Opin. Cell Biol. 8: 795–804.

  • Mahony D, Parry DA and Lees E. . 1998 Oncogene 16: 603–611.

  • Mansour SJ, Matten WT, Hermann AS, Candia JM, Rong S, Fukasawa K, Vande Woude GF and Ahn NG. . 1994 Science 265: 966–970.

  • Marais R, Wynne J and Treisman R. . 1993 Cell 73: 381–393.

  • Matsuoka M, Kato JY, Fisher RP, Morgan DO and Sherr CJ. . 1994 Mol. Cell Biol. 14: 7265–7275.

  • Meloche S, Seuwen K, Pages G and Pouyssegur J. . 1992 Mol. Endocrinol. 6: 845–854.

  • Morgan DO. . 1995 Nature 374: 131–134.

  • Nakielny S, Cohen P, Wu J and Sturgill T. . 1992 EMBO J. 11: 2123–2129.

  • Nigg EA. . 1997 Nature 386: 779–787.

  • Nourse J, Firpo E, Flanagan WM, Coats S, Polyak K, Lee MH, Massague J, Crabtree GR and Roberts JM. . 1994 Nature 372: 570–573.

  • Ohtsubo M, Theodoras AM, Schumacher J, Roberts JM and Pagano M. . 1995 Mol. Cell Biol. 15: 2612–2624.

  • Pages G, Lenormand P, L'Allemain G, Chambard JC, Melocho S and Pouyssegur J. . 1993 Proc. Natl. Acad. Sci. USA 90: 8319–8323.

  • Payne DM, Rossomando AJ, Martino P, Erickson AK, Her JH, Shabanowitz J, Hunt DF, Weber MJ and Sturgill TW. . 1991 EMBO J. 10: 885–892.

  • Pines J and Hunter T. . 1994 EMBO J. 13: 3772–3781.

  • Prosperi E, Stivala LA, Scovassi AI and Bianchi L. . 1997 Eur. J. Histochem. 41: 161–168.

  • Reed SI. . 1997 Cancer Surv. 29: 7–23.

  • Rosenblatt J, Gu Y and Morgan DO. . 1992 Proc. Natl. Acad. Sci. USA 89: 2824–2828.

  • Rossomando A, Wu J, Weber MJ and Sturgill TW. . 1992 Proc. Natl. Acad. Sci. USA 89: 5221–5225.

  • Ruckdeschel K, Machold J, Roggenkamp A, Schubert S, Pierre J, Zumbihl R, Liautard JP, Heesemann J and Rouot B. . 1997 J. Biol. Chem. 272: 15920–15927.

  • Sherr CJ and Roberts JM. . 1995 Genes Dev. 9: 1149–1163.

  • Strausfeld U, Labbe JC, Fesquet D, Cavadore JC, Picard A, Sadhu K, Russell P and Doree M. . 1991 Nature 351: 242–245.

  • Taieb J, Blanchard DA, Auffredou MT, Chaouchi N and Vazquez A. . 1995 J. Immunol. 155: 5623–5630.

  • Tassan JP, Schultz SJ, Bartek J and Nigg EA. . 1994 J. Cell Biol. 127: 467–478.

  • Weinberg RA. . 1995 Cell 81: 323–330.

  • Yang J, Bardes ES, Moore JD, Brennan J, Powers MA and Kornbluth S. . 1998 Genes Dev. 12: 2131–2143.

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Acknowledgements

We would like to thank Dr T Hori and Dr J Pierre for the gift of Kit 225 cells and recombinant Elk1 respectively. We also thank N Avazeri for very useful technical assistance. This work was supported by INSERM and grants from the Association pour la Recherche sur le Cancer (ARC, Villejuif, France). DA Blanchard receives a fellowship from ARC.

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Blanchard, D., Mouhamad, S., Auffredou, MT. et al. Cdk2 associates with MAP Kinase in vivo and its nuclear translocation is dependent on MAP Kinase activation in IL-2-dependent Kit 225 T lymphocytes. Oncogene 19, 4184–4189 (2000). https://doi.org/10.1038/sj.onc.1203761

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