Regulation of the Ras-MAPK Pathway at the Level of Ras and Raf

  • Hark Vikis
  • Kun-Liang Guan
Part of the Genetic Engineering: Principles and Methods book series (GEPM, volume 24)

Abstract

Cells use a variety of intracellular signaling pathways to interpret extracellular signals and translate them into cellular responses. The Ras-mitogen activated protein kinase (MAPK) pathway is a commonly-used intracellular signaling pathway used by eukaryotic cells to regulate such processes as cell growth, differentiation and survival (1,2). At the apex of the pathway is the small GTPase Ras whose activation state regulates a hierarchical three-kinase module comprised of the MAP kinase kinase kinase (MAPKKK), Raf, which phosphorylates and activates the MAP kinase kinase (MAPKK), MEK, which in turn phosphorylates and activates the MAP kinase (MAPK), ERK. How Ras activates Raf is the most complicated and contentious step in the pathway and has not been fully understood. Current findings suggest that activated Ras binds and recruits Raf to the plasma membrane where a coordinated series of phosphorylation events, protein-protein interactions and conformational changes occur to induce full activity. The past few years have led to the identification of new Raf phosphorylation sites that positively and negatively regulate Raf activity. In addition, genetic experiments in Drosophila and C.elegans have identified new proteins that modulate signaling at the level of Ras and Raf.

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References

  1. 1.
    Avruch, J., Khokhlatchev, A., Kyriakis, J. M., Luo, Z., Tzivion, G., Vavvas, D. and Zhang, X. F. (2001) Recent Prog. Horm. Res. 56, 127–155.PubMedGoogle Scholar
  2. 2.
    Katz, M. E. and McCormick, F. (1997) Curr. Opin. Genet. Dev. 7(1), 75–79.PubMedGoogle Scholar
  3. 3.
    Robinson, M. J. and Cobb, M. H. (1997) Curr. Opin. Cell. Biol. 9(2), 180–186.PubMedGoogle Scholar
  4. 4.
    Pearson, G., Robinson, F., Beers Gibson, T., Xu, B.E., Karandikar, M., Berman, K. and Cobb, M. H. (2001) Endocr. Rev. 22(2), 153–183.PubMedGoogle Scholar
  5. 5.
    Hill, C. S. and Treisman, R. (1995) Cell 80(2), 199–211.PubMedGoogle Scholar
  6. 6.
    Lavoie, J. N., L’Allemain, G., Brunet, A., Müller, R. and Pouyssegur, J. (1996) J.Biol. Chem. 271(34), 20608–20616.PubMedGoogle Scholar
  7. 7.
    Roovers, K. and Assoian, R. K. (2000) Bioessays 22(9), 818–826.PubMedGoogle Scholar
  8. 8.
    Bos, J. L. (1989) Cancer Res. 49(17), 4682–4689.PubMedGoogle Scholar
  9. 9.
    Rubin, G. M., Chang, H. C., Karim, F., Laverty, T., Michaud, N. R., Morrison, D. K., Rebay, I., Tang, A., Therrien, M. and Wassarman, D. A. (1997) Cold Spring Harbor Symp. Quant. Biol. 62, 347–352.Google Scholar
  10. 10.
    Sternberg, P. W. and Han, M. (1998) Trends Genet. 14(11), 466–472.PubMedGoogle Scholar
  11. 11.
    Furth, M. E., Aldrich, T. H. and Cordon-Cardo, C. (1987) Oncogene 1(1), 47–58.PubMedGoogle Scholar
  12. 12.
    Leon, J., Guerrero, I. and Pellicer, A. (1987) Mol. Cell. Biol. 7(4), 1535–1540.PubMedGoogle Scholar
  13. 13.
    Umanoff, H., Edelmann, W., Pellicer, A. and Kucherlapati, R. (1995) Proc. Nat.Acad. Sci: U.S.A. 92(5), 1709–1713.Google Scholar
  14. 14.
    Johnson, L., Greenbaum, D., Cichowski, K., Mercer, K., Murphy, E., Schmitt, E., Bronson, R. T., Umanoff, H., Edelmann, W., Kucherlapati, R. and Jacks, T. (1997) Genes Dev. 11(19), 2468–2481.PubMedGoogle Scholar
  15. 15.
    Koera, K., Nakamura, K., Nakao, K., Miyoshi, J., Toyoshima, K., Hatta, T., Otani, H., Aiba, A. and Katsuki, M. (1997) Oncogene 15(10), 1151–1159.PubMedGoogle Scholar
  16. 16.
    Ise, K., Nakamura, K., Nakao, K., Shimizu, S., Harada, H., Ichise, T., Miyoshi, J., Gondo, Y., Ishikawa, T., Aiba, A. and Katsuki, M. (2000) Oncogene 19(26), 2951–2956.PubMedGoogle Scholar
  17. 17.
    Esteban, L. M., Vicario-Abejon, C., Fernandez-Salguero, P., Fernandez-Medarde, A., Swaminathan, N., Yienger, K., Lopez, E., Malumbres, M., McKay, R., Ward, J. M., Pellicer, A. and Santos, E. (2001) Mol. Cell. Biol. 21(5), 1444–1452.PubMedGoogle Scholar
  18. 18.
    Vojtek, A. B. and Der, C. J. (1998) J. Biol. Chem. 273(32), 19925–19928.PubMedGoogle Scholar
  19. 19.
    Hancock, J. F., Magee, A. I., Childs, J. E. and Marshall, C. J. (1989) Cell 57(7),1167–1177.PubMedGoogle Scholar
  20. 20.
    Kikuchi, A. and Williams, L. T. (1994) J. Biol. Chem. 269(31), 20054–20059.PubMedGoogle Scholar
  21. 21.
    Prior, I. A. and Hancock, J. F. (2001) J. Cell Sci. 114(Pt 9), 1603–1608.PubMedGoogle Scholar
  22. 22.
    Choy, E., Chiu, V. K., Silletti, J., Feoktistov, M., Morimoto, T., Michaelson, D., Ivanov, I. E. and Philips, M. R. (1999) Cell 98(1), 69–80.PubMedGoogle Scholar
  23. 23.
    Apolloni, A., Prior, I. A., Lindsay, M., Parton, R. G. and Hancock, J. F. (2000) Mol Cell Biol 20(7), 2475–2487.PubMedGoogle Scholar
  24. 24.
    Rebollo, A., Perez-Sala, D. and Martinez, A. C. (1999) Oncogene 18(35), 4930–4939.PubMedGoogle Scholar
  25. 25.
    Wolfman, J. C. and Wolfman, A. (2000) J. Biol. Chem. 275(25), 19315–19323.PubMedGoogle Scholar
  26. 26.
    Cleveland, J. L., Troppmair, J., Packham, G., Askew, D. S., Lloyd, P., Gonzalez-Garcia, M., Nunez, G., Ihle, J. N. and Rapp, U. R. (1994) Oncogene 9(8), 2217–2226.PubMedGoogle Scholar
  27. 27.
    Roy, S., Luetterforst, R., Harding, A., Apolloni, A., Etheridge, M., Stang, E., Rolls, B., Hancock, J. F. and Parton, R. G. (1999) Nature Cell. Biol. 1(2), 98–105.PubMedGoogle Scholar
  28. 28.
    Scheel, J., Srinivasan, J., Honnert, U., Henske, A. and Kurzchalia, T. V. (1999) Nature Cell. Biol. 1(2), 127–129.PubMedGoogle Scholar
  29. 29.
    Prior, I. A., Harding, A., Yan, J., Sluimer, J., Parton, R. G. and Hancock, J. F. (2001) Nature Cell. Biol. 3(4), 368–375.PubMedGoogle Scholar
  30. 30.
    Liu, P., Ying, Y. and Anderson, R. G. (1997) Proc. Nat. Acad. Sci. U.S.A. 94(25),13666–13670.Google Scholar
  31. 31.
    Hamilton, M. and Wolfman, A. (1998) Oncogene 16(11), 1417–1428.PubMedGoogle Scholar
  32. 32.
    Voice, J. K., Klemke, R. L., Le, A. and Jackson, J. H. (1999) J. Biol. Chem.274(24), 17164–17170.PubMedGoogle Scholar
  33. 33.
    Yan, J., Roy, S., Apolloni, A., Lane, A. and Hancock, J. F. (1998) J. Biol. Chem.273(37), 24052–24056.PubMedGoogle Scholar
  34. 34.
    Walsh, A. B. and Bar-Sagi, D. (2001) J. Biol. Chem. 276(19), 15609–15615.PubMedGoogle Scholar
  35. 35.
    Finney, R. E. and Bishop, J. M. (1993) Science 260(5113), 1524–1527.PubMedGoogle Scholar
  36. 36.
    Cohen, J. B. and Levinson, A. D. (1988) Nature 334(6178), 119–124.PubMedGoogle Scholar
  37. 37.
    Guerrero, I., Villasante, A., Corces, V. and Pellicer, A. (1985) Proc. Nat. Acad.Sci. U.S.A. 82(23), 7810–7814.Google Scholar
  38. 38.
    Riou, G., Barrois, M., Sheng, Z. M., Duvillard, P. and Lhomme, C. (1988) Oncogene 3(3), 329–333.PubMedGoogle Scholar
  39. 39.
    Diamond, L. E., Guerrero, I. and Pellicer, A. (1988) Mol. Cell. Biol. 8(5), 2233–2236.PubMedGoogle Scholar
  40. 40.
    Bremner, R, and Balmain, A. (1990) Cell 61(3), 407–417.PubMedGoogle Scholar
  41. 41.
    Buchmann, A., Ruggeri, B., Klein-Szanto, A. J. and Balmain, A. (1991) Cancer Res. 51(15), 4097–4101.PubMedGoogle Scholar
  42. 42.
    Hegi, M. E., Devereux, T. R., Dietrich, W. F., Cochran, C. J., Lander, E. S., Foley, J. F., Maronpot, R. R., Anderson, M. W. and Wiseman, R. W. (1994) Cancer Res. 54(23), 6257–6264.PubMedGoogle Scholar
  43. 43.
    Zhang, Z., Wang, Y., Vikis, H. G., Johnson, L., Liu, G., Li, J., Anderson, M. W., Sills, R. C., Hong, H. L., Devereux, T. R., Jacks, T., Guan, K. L. and You, M. (2001) Nature Genet. 29(1), 25–33.PubMedGoogle Scholar
  44. 44.
    Feig, L. A. and Cooper, G. M. (1988) Mol. Cell. Biol. 8(8), 3235–3243.PubMedGoogle Scholar
  45. 45.
    John, J., Rensland, H., Schlichting, I., Vetter, I., Borasio, G. D., Goody, R. S. and Wittinghofer, A. (1993) J. Biol. Chem. 268(2), 923–929.PubMedGoogle Scholar
  46. 46.
    Stewart, S. and Guan, K. L. (2000) J. Biol. Chem. 275(12), 8854–8862.PubMedGoogle Scholar
  47. 47.
    Kolch, W., Heidecker, G., Lloyd, P. and Rapp, U. R. (1991) Nature 349(6308),426–428.PubMedGoogle Scholar
  48. 48.
    Vojtek, A. B., Hollenberg, S. M. and Cooper, J. A. (1993) Cell 74(1), 205–214.PubMedGoogle Scholar
  49. 49.
    Van Aelst, L., Barr, M., Marcus, S., Polverino, A. and Wigler, M. (1993) Proc.Nat. Acad. Sci. U.S.A. 90(13), 6213–6217.Google Scholar
  50. 50.
    Zhang, X. F., Settleman, J., Kyriakis, J. M., Takeuchi-Suzuki, E., Elledge, S. J., Marshall, M. S., Bruder, J. T., Rapp, U. R. and Avruch, J. (1993) Nature 364(6435), 308–313.PubMedGoogle Scholar
  51. 51.
    Leevers, S. J., Paterson, H. F. and Marshall, C. J. (1994) Nature 369(6479), 411–414.PubMedGoogle Scholar
  52. 52.
    Morrison, D. K. and Cutler, R. E. (1997) Curr. Opin. Cell. Biol. 9(2), 174–179.PubMedGoogle Scholar
  53. 53.
    Hagemann, C. and Rapp, U. R. (1999) Exp. Cell Res. 253(1), 34–46.PubMedGoogle Scholar
  54. 54.
    Stokoe, D., Macdonald, S. G., Cadwallader, K., Symons, M. and Hancock, J. F.(1994) Science 264(5164), 1463–1467.PubMedGoogle Scholar
  55. 55.
    Mineo, C., Anderson, R. G. and White, M. A. (1997) J. Biol. Chem. 272(16),10345–10348.PubMedGoogle Scholar
  56. 56.
    Ghosh, S., Strum, J. C., Sciorra, V. A., Daniel, L. and Bell, R. M. (1996) J. Biol.Chem. 271(14), 8472–8480.PubMedGoogle Scholar
  57. 57.
    Farrar, M. A., Alberol, I. and Perlmutter, R. M. (1996) Nature 383(6596), 178–181PubMedGoogle Scholar
  58. 58.
    Luo, Z., Tzivion, G., Belshaw, P. J., Vavvas, D., Marshall, M. and Avruch, J.(1996) Nature 383(6596), 181–185.PubMedGoogle Scholar
  59. 59.
    Weber, C. K., Slupsky, J. R., Kalmes, H. A. and Rapp, U. R. (2001) Cancer Res.61(9), 3595–3598.PubMedGoogle Scholar
  60. 60.
    Kolch, W. (2000) Biochem. J. 351 Pt 2, 289–305.Google Scholar
  61. 61.
    Dent, P., Haser, W., Haystead, T. A., Vincent, L. A., Roberts, T. M. and Sturgill, T. W. (1992) Science 257(5075), 1404–1407.PubMedGoogle Scholar
  62. 62.
    Chuang, E., Barnard, D., Hettich, L., Zhang, X. F., Avruch, J. and Marshall, M. S.(1994) Mol. Cell. Biol. 14(8), 5318–5325.PubMedGoogle Scholar
  63. 63.
    Hu, C. D., Kariya, K., Tamada, M., Akasaka, K., Shirouzu, M., Yokoyama, S. and Kataoka, T. (1995) J. Biol. Chem. 270(51), 30274–30277.PubMedGoogle Scholar
  64. 64.
    Luo, Z., Diaz, B., Marshall, M. S. and Avruch, J. (1997) Mol. Cell. Biol. 17(1),46–53.PubMedGoogle Scholar
  65. 65.
    Drugan, J. K., Khosravi-Far, R., White, M. A., Der, C. J., Sung, Y. J., Hwang, Y. W. and Campbell, S. L. (1996) J. Biol. Chem. 271(1), 233–237.PubMedGoogle Scholar
  66. 66.
    Inouye, K., Mizutani, S., Koide, H. and Kaziro, Y. (2000) J. Biol. Chem. 275(6),3737–3740.PubMedGoogle Scholar
  67. 67.
    Sendoh, H., Hu, C. D., Wu, D., Song, C., Yamawaki-Kataoka, Y., Kotani, J., Okada, T., Shima, F., Kariya, K. and Kataoka, T. (2000) Biochem. Biophys. Res. Commun. 271(3), 596–602.Google Scholar
  68. 68.
    Lei, M., Lu, W., Meng, W., Parrini, M. C., Eck, M. J., Mayer. B. J. and Harrison. S. C. (2000) Cell 102(3), 387–397.PubMedGoogle Scholar
  69. 69.
    Buchwald, G., Hostinova, E., Rudolph, M. G., Kraemer, A., Sickmann, A., Meyer, H. E., Scheffzek, K. and Wittinghofer, A. (2001) Mol. Cell. Biol. 21(15), 5179–5189.PubMedGoogle Scholar
  70. 70.
    Li, W., Chong, H. and Guan, K. L. (2001) J. Biol. Chem. 276(37), 34728–34737.PubMedGoogle Scholar
  71. 71.
    King, A. J., Sun, H., Diaz, B., Barnard, D., Miao, W., Bagrodia, S. and Marshall, M. S. (1998) Nature 396(6707), 180–183.PubMedGoogle Scholar
  72. 72.
    Nimnual, A. S., Yatsula, B. A. and Bar-Sagi, D. (1998) Science 279(5350). 560–563.PubMedGoogle Scholar
  73. 73.
    Han, J., Luby-Phelps, K., Das, B., Shu, X., Xia, Y., Mosteller, R. D., Krishna, U. M., Falck, J. R., White, M. A. and Brock, D. (1998) Science 279(5350), 558–560.PubMedGoogle Scholar
  74. 74.
    Fabian, J. R., Daar, I. O. and Morrison, D. K. (1993) Mol. Cell. Biol. 13(11), 7170–7179.PubMedGoogle Scholar
  75. 75.
    Marais, R., Light, Y., Paterson, H. F. and Marshall, C. J. (1995) EMBO J. 14(13),3136–3145.PubMedGoogle Scholar
  76. 76.
    Barnard, D., Diaz, B., Clawson, D. and Marshall, M. (1998) Oncogene 17(12),1539–1547.PubMedGoogle Scholar
  77. 77.
    Mason, C. S., Springer, C. J., Cooper, R. G., Superti-Furga, G., Marshall, C. J. and Marais, R. (1999) EMBO J. 18(8), 2137–2148.PubMedGoogle Scholar
  78. 78.
    Marais, R., Light, Y., Paterson, H. F., Mason, C. S. and Marshall, C. J. (1997) J.Biol. Chem. 272(7), 4378–4383.PubMedGoogle Scholar
  79. 79.
    Chong, H., Lee, J. and Guan, K. L. (2001) EMBO J. 20(14), 3716–3727.PubMedGoogle Scholar
  80. 80.
    Zhang, B. H. and Guan, K. L. (2000) EMBO J. 19(20), 5429–5439.PubMedGoogle Scholar
  81. 81.
    Kolch, W., Heidecker, G., Kochs, G., Hummel, R., Vahidi, H., Mischak, H., Finkenzeller, G., Marme, D. and Rapp, U. R. (1993) Nature 364(6434), 249–252.PubMedGoogle Scholar
  82. 82.
    Carroll, M. P. and May, W. S. (1994) J. Biol. Chem. 269(2), 1249–1256.PubMedGoogle Scholar
  83. 83.
    Sozeri, O., Vollmer, K., Liyanage, M., Frith, D., Kour, G., Mark, G. E., 3rd and Stabel, S. (1992) Oncogene 7(11), 2259–2262.PubMedGoogle Scholar
  84. 84.
    Schonwasser, D. C., Marais, R. M., Marshall, C. J. and Parker, P. J. (1998) Mol.Cell. Biol. 18(2), 790–798.PubMedGoogle Scholar
  85. 85.
    Marais, R., Light, Y., Mason, C., Paterson, H., Olson, M. F. and Marshall, C. J.(1998) Science 280(5360), 109–112.PubMedGoogle Scholar
  86. 86.
    Wu, J., Dent, P., Jelinek, T., Wolfman, A., Weber, M. J. and Sturgill, T. W.(1993) Science 262(5136), 1065–1069.PubMedGoogle Scholar
  87. 87.
    Morrison, D. K., Heidecker, G., Rapp, U. R. and Copeland, T. D. (1993) J. Biol.Chem. 268(23), 17309–17316.PubMedGoogle Scholar
  88. 88.
    Schramm, K., Niehof, M., Radziwill, G., Rommel, C. and Moelling, K. (1994)Biochem. Biophys. Res. Commun. 201(2), 740–747.Google Scholar
  89. 89.
    Ramstad, C., Sundvold, V., Johansen, H. K. and Lea, T. (2000) Cell Signal 12(8),557–563.PubMedGoogle Scholar
  90. 90.
    de Rooij, J., Zwartkruis, F. J., Verheijen, M. H., Cool, R. H., Nijman, S. M., Wittinghofer, A. and Bos, J. L. (1998) Nature 396(6710), 474–477.PubMedGoogle Scholar
  91. 91.
    Vossler, M. R., Yao, H., York, R. D., Pan, M. G., Rim, C. S. and Stork, P. J.(1997) Cell 89(1), 73–82.PubMedGoogle Scholar
  92. 92.
    Sidovar, M. F., Kozlowski, P., Lee, J. W., Collins, M. A., He, Y. and Graves, L. M. (2000) J. Biol. Chem. 275(37), 28688–28694.PubMedGoogle Scholar
  93. 93.
    MacNicol, M. C. and MacNicol, A. M. (1999) J. Biol. Chem. 274(19), 13193–13197.PubMedGoogle Scholar
  94. 94.
    Zimmermann, S. and Moelling, K. (1999) Science 286(5445), 1741–1744.PubMedGoogle Scholar
  95. 95.
    Rommel, C., Clarke, B. A., Zimmermann, S., Nunez, L., Rossman, R., Reid, K., Moelling, K., Yancopoulos, G. D. and Glass, D. J. (1999) Science 286(5445), 1738–1741.PubMedGoogle Scholar
  96. 96.
    Rommel, C., Radziwill, G., Lovric, J., Noeldeke, J., Heinicke, T., Jones, D., Aitken, A. and Moelling, K. (1996) Oncogene 12(3), 609–619.PubMedGoogle Scholar
  97. 97.
    Michaud, N. R., Fabian, J. R., Mathes, K. D. and Morrison, D. K. (1995) Mol. Cell. Biol. 15(6), 3390–3397.PubMedGoogle Scholar
  98. 98.
    Guan, K. L., Figueroa, C., Brtva, T. R., Zhu, T., Taylor, J., Barber, T. D. and Vojtek, A. B. (2000) J. Biol. Chem. 275(35), 27354–27359.PubMedGoogle Scholar
  99. 99.
    Zhang, B. H., Tang, E. D., Zhu, T., Greenberg, M. E., Vojtek, A. B. and Guan, K. L. (2001) J. Biol. Chem. 276(34), 31620–31626.PubMedGoogle Scholar
  100. 100.
    Perrotti, N., He, R. A., Phillips, S. A., Haft, C. R. and Taylor, S. I. (2001) J. Biol.Chem. 276(12), 9406–9412.PubMedGoogle Scholar
  101. 101.
    Sieburth, D. S., Sundaram, M., Howard, R. M. and Han, M. (1999) Genes Dev.13(19), 2562–2569.PubMedGoogle Scholar
  102. 102.
    Abraham, D., Podar, K., Pacher, M., Kubicek, M., Wetzel, N., Hemmings, B. A., Dilworth, S. M., Mischak, H., Kolch, W. and Baccarini, M. (2000) J. Biol. Chem. 275(29), 22300–22304.PubMedGoogle Scholar
  103. 103.
    Jaumot, M. and Hancock, J. F. (2001) Oncogene 20(30), 3949–3958.PubMedGoogle Scholar
  104. 104.
    Zheng, C. F. and Guan, K. L. (1994) EMBO J. 13(5), 1123–1131.PubMedGoogle Scholar
  105. 105.
    Alessi, D. R., Saito, Y., Campbell, D. G., Cohen, P., Sithanandam, G., Rapp, U., Ashworth, A., Marshall, C. J. and Cowley, S. (1994) EMBO J. 13(7), 1610–1619.PubMedGoogle Scholar
  106. 106.
    Cowley, S., Paterson, H., Kemp, P. and Marshall, C. J. (1994) Cell 77(6), 841–852.PubMedGoogle Scholar
  107. 107.
    Catling, A. D., Schaeffer, H. J., Reuter, C. W., Reddy, G. R. and Weber, M. J.(1995) Mol. Cell. Biol. 15(10), 5214–5225.PubMedGoogle Scholar
  108. 108.
    Schaeffer, H. J., Catling, A. D., Eblen, S. T., Collier, L. S., Krauss, A. and Weber, M. J. (1998) Science 281(5383), 1668–1671.PubMedGoogle Scholar
  109. 109.
    Salmerón, A., Ahmad, T. B., Carlile, G. W., Pappin, D., Narsimhan, R. P. and Ley, S. C. (1996) EMBO J. 15(4), 817–826.PubMedGoogle Scholar
  110. 110.
    Pham, C. D., Arlinghaus, R. B., Zheng, C. F., Guan, K. L. and Singh, B. (1995) Oncogene 10(8), 1683–1688.PubMedGoogle Scholar
  111. 111.
    Payne, D. M., Rossomando, A. J., Martino, P., Erickson, A. K., Her, J. H., Shabanowitz, J., Hunt, D. F., Weber, M. J. and Sturgill, T. W. (1991) EMBO J. 10(4), 885–892.PubMedGoogle Scholar
  112. 112.
    Reszka, A. A., Bulinski, J. C., Krebs, E. G. and Fischer, E. H. (1997) Mol. Biol.Cell 8(7), 1219–1232.PubMedGoogle Scholar
  113. 113.
    Robinson, M. J., Stippec, S. A., Goldsmith, E., White, M. A. and Cobb, M. H.(1998) Curr. Biol. 8(21), 1141–1150.PubMedGoogle Scholar
  114. 114.
    Tolwinski, N. S., Shapiro, P. S., Goueli, S. and Ahn, N. G. (1999) J. Biol, Chem.274(10), 6168–6174.Google Scholar
  115. 115.
    Adachi, M., Fukuda, M. and Nishida, E. (2000) J. Cell Biol. 148(5), 849–856.PubMedGoogle Scholar
  116. 116.
    Wartmann, M. and Davis, R. J. (1994) J. Biol. Chem. 269(9), 6695–6701.PubMedGoogle Scholar
  117. 117.
    Morrison, D. K. (1995) Mol. Reprod. Dev. 42(4), 507–514.PubMedGoogle Scholar
  118. 118.
    Thorson, J. A., Yu, L. W., Hsu, A. L., Shih, N. Y., Graves, P. R., Tanner, J. W., Allen, P. M., Piwnica-Worms, H. and Shaw, A. S. (1998) Mol. Cell. Biol. 18(9), 5229–5238.PubMedGoogle Scholar
  119. 119.
    Roy, S., McPherson, R. A., Apolloni, A., Yan, J., Lane, A., Clyde-Smith, J. and Hancock, J. F. (1998) Mol. Cell. Biol. 18(7), 3947–3955.PubMedGoogle Scholar
  120. 120.
    Tzivion, G., Luo, Z. and Avruch, J. (1998) Nature 394(6688), 88–92.PubMedGoogle Scholar
  121. 121.
    Mischak, H., Seitz, T., Janosch, P., Eulitz, M., Steen, H., Schellerer, M., Philipp, A. and Kolch, W. (1996) Mol. Cell. Biol. 16(10), 5409–5418.PubMedGoogle Scholar
  122. 122.
    Therrien, M., Chang, H. C., Solomon, N. M., Karim, F. D., Wassarman, D. A. and Rubin, G. M. (1995) Cell 83(6), 879–888.PubMedGoogle Scholar
  123. 123.
    Sundaram, M. and Han, M. (1995) Cell 83(6), 889–901.PubMedGoogle Scholar
  124. 124.
    Kornfeld, K., Horn, D. B. and Horvitz, H. R. (1995) Cell 83(6), 903–913.PubMedGoogle Scholar
  125. 125.
    Zhang, Y., Yao, B., Delikat, S., Bayoumy, S., Lin, X. H., Basu, S., McGinley, M., Chan-Hui, P. Y., Lichenstein, H. and Kolesnick, R. (1997) Cell 89(1), 63–72.PubMedGoogle Scholar
  126. 126.
    Morrison, D. K. (2001) J. Cell Sci. 114(Pt 9), 1609–1612.PubMedGoogle Scholar
  127. 127.
    Stewart, S., Sundaram, M., Zhang, Y., Lee, J., Han, M. and Guan, K. L. (1999) Mol. Cell. Biol. 19(8), 5523–5534.PubMedGoogle Scholar
  128. 128.
    Yu, W., Fantl, W. J., Harrowe, G. and Williams, L. T. (1998) Curr. Biol. 8(1), 56–64.PubMedGoogle Scholar
  129. 129.
    Cacace, A. M., Michaud, N. R., Therrien, M., Mathes, K., Copeland, T., Rubin, G. M. and Morrison, D. K. (1999) Mol. Cell. Biol. 19(1), 229–240.PubMedGoogle Scholar
  130. 130.
    Xing, H. R., Lozano, J. and Kolesnick, R. (2000) J. Biol. Chem. 275(23), 17276–17280.PubMedGoogle Scholar
  131. 131.
    Xing, H. R. and Kolesnick, R. (2001) J. Biol. Chem. 276(13), 9733–9741.PubMedGoogle Scholar
  132. 132.
    Therrien, M., Wong, A. M. and Rubin, G. M. (1998) Cell 95(3), 343–353.PubMedGoogle Scholar
  133. 133.
    Therrien, M., Wong, A. M., Kwan, E. and Rubin, G. M. (1999) Proc. Nat. Acad.Sci. U.S.A. 96(23), 13259–13263.Google Scholar
  134. 134.
    Sieburth, D. S., Sun, Q. and Han, M. (1998) Cell 94(1), 119–130.PubMedGoogle Scholar
  135. 135.
    Selfors, L. M., Schutzuran, J. L., Borland, C. Z. and Stern, M. J. (1998) Proc. Nat.Acad. Sci. U.S.A. 95(12), 6903–6908.Google Scholar
  136. 136.
    Li, W., Han, M. and Guan, K. L. (2000) Genes Dev. 14(8), 895–900.PubMedGoogle Scholar
  137. 137.
    Yeung, K., Seitz, T., Li, S., Janosch, P., McFerran, B., Kaiser, C., Fee, F., Katsanakis, K. D., Rose, D. W., Mischak, H., Sedivy, J. M. and Kolch, W. (1999) Nature 401(6749), 173–177.PubMedGoogle Scholar
  138. 138.
    Yeung, K., Janosch, P., McFerran, B., Rose, D. W., Mischak, H., Sedivy, J. M. and Kolch, W. (2000) Mol. Cell. Biol. 20(9), 3079–3085.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Hark Vikis
    • 1
  • Kun-Liang Guan
    • 1
    • 2
  1. 1.Department of Biological ChemistryUniversity of Michigan Medical School
  2. 2.Institute of GerontologyUniversity of MichiganAnn Arbor

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