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Constitutively Active STATs and Cellular Transformation

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Signal Transducers and Activators of Transcription (STATs)

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Abstract

The JAK/STAT pathway is activated by more than 40 ligands including cytokines, growth factors, non-receptor tyrosine kinases and G-proteins. Ligand binding leads to receptor dimerization, activation of a tyrosine kinase (typically a JAK), phosphorylation of the intracytoplasmic portion of the receptor and docking of STATs to the tyrosine phosphorylated receptor. STAT phosphorylation occurs either by an intrinsic tyrosine kinase or via receptor associated JAKs. The phosphorylated STATs form homo- or heterodimers, translocate to the nucleus, bind to specific sites on DNA and activate transcription (for reviews see 1–5). This process is negatively regulated by a number of molecules. For example, the SHP-2 phophatase can inhibit STAT activation by de-phosphorylating the JAKs or Stats (6–12). SOCS proteins can bind to and inhibit the activity of JAK directly or block the JAKSTAT interaction (13, 14). In the nucleus, DNA binding of dimerized STATs can be inhibited by the PIAS proteins (14–16) or by tyrosine dephosphorylation through nuclear tyrosine phosphatases such as TC45 (17–19).

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References

  1. Bromberg, J., Chens, X. (2001) Meth Enzymol 333 138–151

    Google Scholar 

  2. Bromberg, J. (2002) J Clin Invest 109, 1139–1142

    PubMed  CAS  Google Scholar 

  3. Bromberg, J. (2001) BioEssays 23, 161–169

    CAS  Google Scholar 

  4. Darnell, J.E., Jr. (1997) Science 277, 1630–1635

    Article  PubMed  CAS  Google Scholar 

  5. Levy, D.E. and Darnell, J.E., Jr. (2002) Nat Rev Mol Cell Biol 3, 651–662

    Article  PubMed  CAS  Google Scholar 

  6. David, M., Chen, H.E., Goelz, S., Larner, A.C. and Neel, B.G. (1995) Mol Cell Biol 15, 7050–7058

    PubMed  CAS  Google Scholar 

  7. Chen, Y., Wen, R., Yang, S., Schuman, J., Zhang, E.E., Yi, T., Feng, G.S and Wang, D. (2003) J Biol Chem 278: 16520–16527

    Article  PubMed  CAS  Google Scholar 

  8. Wu, T.R., Hong, Y.K., Wang, X.D., Ling, M.Y., Dragoi, A.M., Chung, A.S., Campbell, A.G., Han, Z.Y., Feng, G.S. and Chin, Y.E. (2002) J Biol Chem 277, 47572–47580

    Article  PubMed  CAS  Google Scholar 

  9. Klingmuller, U., Lorenz, U., Cantley, L.C., Neel, B.G. and Lodish H.F. (1995) Cell 80, 729–38.

    Article  PubMed  CAS  Google Scholar 

  10. Irie-Sasaki, J., Sasaki, T., Matsumoto, W., Opavsky, A., Cheng, M., Welstead, G., Griffiths, E., Krawczyk, C., Richardson, C.D., Aitken, K., Iscove, N., Koretzky, G., Johnson, P., Liu, P., Rothstein, D.M. and Penninger J.M. (2001) Nature 409, 49–354

    Article  Google Scholar 

  11. Yu, C.L., Jin, Y.J. and Burakoff S.J. (2000) J Biol Chem 275, 599–604

    Article  PubMed  CAS  Google Scholar 

  12. Aoki, N. and Matsuda, T. (2000) J Biol Chem 275, 39718–39726.

    Article  PubMed  CAS  Google Scholar 

  13. Chen, X.P., Losman, J.A. and Rothman P. (2000) Immunity 3, 287–290

    Article  Google Scholar 

  14. Starr R. and Hilton D.J. (1999) Bioessays 21, 47–52

    Article  PubMed  CAS  Google Scholar 

  15. Liu, B., Liao, J., Rao, X., Kushner, S.A., Chung, C.D., Chang, D.D. and Shuai K. (1998) Proc Natl Acad Sci USA 95, 10626–10631

    Article  PubMed  CAS  Google Scholar 

  16. Chung, C.D., Liao, J., Liu, B., Rao, X., Jay, P., Berta, P. and Shuai, K. (1997) Science 278, 1803–1805

    Article  PubMed  CAS  Google Scholar 

  17. Ten Hoeve, J., de Jesus Ibarra-Sanchez, M., Fu, Y., Zhu, W., Tremblay, M., David, M. and Shuai K. (2002) Mol Cell Biol 22, 5662–5668

    Article  PubMed  Google Scholar 

  18. Aoki, N. and Matsuda, T. (2002) Mol Endocrinol 16, 58–69

    Article  PubMed  CAS  Google Scholar 

  19. Haspel, R.L. and Darnell, J.E., Jr. (1999) Proc Natl Acad Sci USA 96, 10188–10193.

    Article  PubMed  CAS  Google Scholar 

  20. Duyster J., Bai R.Y., Morris S.W. (2001) Oncogene 20, 5623–5637

    Article  PubMed  CAS  Google Scholar 

  21. Zhang, Q., Raghunath, P.N., Xue, L., Majewski, M., Carpentieri, D.F., Odum, N., Morris, S., Skorski, T. and Wasik M.A. (2002) J Immunol 168, 466–474

    PubMed  CAS  Google Scholar 

  22. Zamo, A., Chiarle, R., Piva, R., Howes, J., Fan, Y., Chilosi, M., Levy, D.E., and Inghirami G. (2002) Oncogene. 21, 1038–1047

    Article  PubMed  CAS  Google Scholar 

  23. Shuai, K., Halpern, J., ten Hoeve, J., Rao, X. and Sawyers C.L. (1996) Oncogene 13, 247–54

    PubMed  CAS  Google Scholar 

  24. Nieborowska-Skorska, M., Wasik, M.A., Slupianek, A., Salomoni, P., Kitamura, T., Calabretta, B. and Skorski T. (1999) J Exp Med 189, 1229–1242

    Article  PubMed  CAS  Google Scholar 

  25. Migone,T.S., Lin,J.X., Cereseto,A., Mulloy,J.C., O’Shea,J.J., Franchini,G. and Leonard,W.J. (1995) Science. 269, 79–81

    Article  Google Scholar 

  26. Takemoto, S., Mulloy, J.C., Cereseto, A., Migone, T.S., Patel, B.K., Matsuoka, M., Yamaguchi, K., Takatsuki, K., Kamihira, S., White, J.D., Leonard, W.J., Waldmann, T. and Franchini, G. 91997) Proc Natl Acad Sci USA 94, 13897–13902

    Google Scholar 

  27. Schwaller, J., Parganas, E., Wang, D., Cain, D., Aster, J.C., Williams, I.R., Lee, C.K., Gerthner, R., Kitamura, T., Frantsve, J, Anastasiadou, E., Loh, M.L., Levy, D.E., Ihle, J.N. and Gilliland D.G. (2000) Mol Cell 6, 693–704

    Article  PubMed  CAS  Google Scholar 

  28. Ning, Z.Q., Li, J., McGuinness, M., Arceci, R.J. (2001) Oncogene 20, 4528–4536

    Google Scholar 

  29. Nielsen, M., Kaltoft, K., Nordahl, M., Ropke, C., Geisler, C., Mustelin, T., Dobson, P., Svejgaard, A. and Odum N. (1997) Proc Natl Acad Sci USA 94, 6764–6769

    Article  PubMed  CAS  Google Scholar 

  30. Nielsen, M., Kaestel, C.G., Eriksen, K.W., Woetmann, A., Stokkedal, T., Kaltoft, K., Geisler, C., Ropke, C. and Odum, N. (1999) Leukemia 13, 735–738

    Article  PubMed  CAS  Google Scholar 

  31. Catlett-Falcone, R., Landowski, T. H., Oshiro, M. M., Turkson, J., Levitzki, A., Savino, R., Ciliberto, G., Moscinski, L., Fernandez-Luna, J. L., Nunez, G., Dalton, W. S. and Jove R. (1999) Immunity 10, 105–115

    Article  PubMed  CAS  Google Scholar 

  32. Puthier, D., Bataille, R. and Amiot, M. (1999) Eur J Immunol 29, 3945–3950

    Article  PubMed  CAS  Google Scholar 

  33. Grandis, J. R., Drenning, S. D., Zeng, Q., Watkins, S. C., Melhem, M. F., Endo, S., Johnson, D. E., Huang, L., He, Y. and Kims, J. D. (2000) Proc Natl Acad Sci USA 97, 4227–4232

    Article  PubMed  CAS  Google Scholar 

  34. Grandis, J.R., Drenning, S.D., Chakraborty, A., Zhou, M.Y., Zeng, Q., Pitt, A.S. and Tweardy D.J. (1998) J Clin Invest 102, 1385–1392

    Article  PubMed  CAS  Google Scholar 

  35. Mora, L.B., Buettner, R., Seigne, J., Diaz, J., Ahmad, N., Garcia, R., Bowman, T., Falcone, R., Fairclough, R., Cantor, A., Muro-Cacho, C., Livingston, S., Karras, J., Pow-Sang, J. and Jove R. (2002) Cancer Res 62, 6659–6666

    PubMed  CAS  Google Scholar 

  36. Li, L. and Shaw, P.E. (2002) J Biol Chem 277, 17397–17405

    Article  PubMed  CAS  Google Scholar 

  37. Garcia, R., Bowman, T.L., Niu, G., Yu, H., Minton, S., Muro-Cacho, C.A., Cox, C.E., Falcone, R., Fairclough, R., Parsons, S., Laudano, A., Gazit, A., Levitzki, A., Kraker, A. and Jove, R. (200 1) Oncogene 20, 2499–2513

    Google Scholar 

  38. Garcia, R., Yu, C.L., Hudnall, A., Catlett, R., Nelson, K.L., Smithgall, T., Fujita, D.J., Ethier, S.P. and Jove, R. (1997) Cell Growth Differ 8, 1267–1276

    PubMed  CAS  Google Scholar 

  39. Akira, S. (2000) Oncogene 19, 2607–2611

    Article  PubMed  CAS  Google Scholar 

  40. Bromberg, J., Horvath, C.M., Besser, D., Lathem, W.W. and Darnell, J.E. Jr. (1998) Mol Cell Biol 18, 2553–2558

    PubMed  CAS  Google Scholar 

  41. Besser, D., Bromberg, J.F., Darnell, J.E., Jr. and Hanafusa, H. (1999) Mol Cell Biol 19, 1401–1409.

    Google Scholar 

  42. Schuringa, J.J., Wojtachnio, K., Hagens, W., Vellenga, E., Buys, C.H., Hofstra, R. and Kruijer, W. (2001) Oncogene 20, 5350–5358

    Article  PubMed  CAS  Google Scholar 

  43. Ram, P.T., Horvath, C.M., Iyengar, R. (2000) Science 287, 142–144

    Article  PubMed  CAS  Google Scholar 

  44. Yu, C.L., Jove, R. and Burakoff, S.J. (1997) J Immunol 159, 5206–5210

    PubMed  CAS  Google Scholar 

  45. Lund, T.C., Prator, P.C., Medveczky, M.M. and Medveczky, P.G. (1999) J Virol 73, 1689–1694

    PubMed  CAS  Google Scholar 

  46. Rottapel, R., Ilangumaran, S., Neale, C., La Rose, J., Ho, J.M., Nguyen, M.H., Barber, D., Dubreuil, P. and de Sepulveda, P. (2002) Oncogene 21, 4351–4362

    Article  PubMed  CAS  Google Scholar 

  47. Yoshikawa, H., Matsubara, K., Qian, G.S., Jackson, P., Groopman, J.D., Manning, J.E., Harris, C.C. and Herman, J.G. (2001) Nat Genet 28, 29–35

    PubMed  CAS  Google Scholar 

  48. Galm, O., Yoshikawa, H., Esteller, M. Osieka, R. and Herman J.G. (2002) Blood 101, 2784–2788

    Google Scholar 

  49. Onishi, M., Nosaka, T., Misawa, K., Mui, A.L., Gorman, D., McMahon, M., Miyajima, A. and Kitamura, T. (1998) Mol Cell Biol 18, 3871–3879

    PubMed  CAS  Google Scholar 

  50. Spiekermann, K., Pau, M., Schwab, R., Schmieja, K., Franzrahe, S. and Hiddemann, W. (2002) Exp Hematol 30, 262–271

    Article  PubMed  CAS  Google Scholar 

  51. Bromberg, J., Wrzeszczynska, M., Devgan, G., Zhao, Y., Albanese, C., Pestell, R. and Darnell, J. E., Jr. (1999) Cell 98, 295–303

    Article  PubMed  CAS  Google Scholar 

  52. Wei, D., Le, X., Zheng, L., Wang, L., Frey, J.A., Gao, A.C., Peng, Z., Huang, S., Xiong, H.Q., Abbruzzese, J.L. and Xie, K. (2003) Oncogene 22, 319–329

    Article  PubMed  CAS  Google Scholar 

  53. Niu, G., Wright, K.L., Huang, M., Song, L., Haura, E., Turkson, J., Zhang, S., Wang, T., Sinibaldi, D., Coppola, D., Heller, R., Ellis, L.M., Karras, J., Bromberg, J., Pardoll, D., Jove, R. and Yu H. (2002) Oncogene 21, 2000–2008

    Article  PubMed  CAS  Google Scholar 

  54. Shen, Y., Devgan, G., Darnell, J.E., Jr. and Bromberg, J.F. (2001) Proc Natl Acad Sci USA 98, 1543–1548

    Article  PubMed  CAS  Google Scholar 

  55. Epling-Burnette, P.K., Liu, J.H., Catlett-Falcone, R., Turkson, J., Oshiro, M, Kothapalli, R., Li, Y., Wang, J.M., Yang-Yen, H.F., Karras, J., Jove, R., Loughran, T.P., Jr. (2001) J Clin Invest 107, 351–362

    Article  PubMed  CAS  Google Scholar 

  56. Nielsen, M., Kaestel, C.G., Eriksen, K.W., Woetmann, A., Stokkedal, T., Kaltoft, K., Geisler, C., Ropke, C. and Odum, N. (1999) Leukemia 13, 735–738

    Article  PubMed  CAS  Google Scholar 

  57. Ivanov, V.N., Bhoumik, A., Krasilnikov, M., Raz, R., Owen-Schaub, L.B., Levy, D., Horvath, C.M. and Ronai Z. (2001) Mol Cell 7, 517–528

    Article  PubMed  CAS  Google Scholar 

  58. Bowman, T., Broome, M.A., Sinibaldi, D., Wharton, W., Pledger, W.J., Sedivy, J.M., Irby, R., Yeatman, T., Courtneidge, S.A. and Jove, R. (2001) Proc Natl Acad Sci USA 98, 7319–24

    Google Scholar 

  59. Schaefer, L.K., Ren, Z., Fuller, G.N. and Schaefer, T.S. (2002) Oncogene 21, 2058–2065

    Article  PubMed  CAS  Google Scholar 

  60. Meraz, M.A., White, J.M., Sheehan, K.C., Bach, E.A., Rodig, S.J., Dighe, A.S., Kaplan, D.H., Riley, J.K., Greenlund, A.C., Campbell, D., Carver-Moore, K., DuBois, R.N., Clark, R., Aguet, M. and Schreiber, R.D. (1996) Cell 84, 431–442

    Article  PubMed  CAS  Google Scholar 

  61. Durbin, J.E., Hackenmiller, R., Simon, M.C. and Levy, D.E. (1996) Cell 84, 443–450

    Article  PubMed  CAS  Google Scholar 

  62. Kaplan, D.H., Shankaran, V., Dighe, A.S., Stockert, E., Aguet, M., Old, L.J. and Schreiber, R.D. (1998) Proc Natl Acad Sci USA 95, 7556–7561

    Article  PubMed  CAS  Google Scholar 

  63. Huang, S., Bucana, C.D., Van Arsdall, M. and Fidler, I.J. (2002) Oncogene 21, 2504–2512

    Article  PubMed  CAS  Google Scholar 

  64. Bromberg, J.F., Horvath, C.M., Wen, Z., Schreiber, R.D. and Darnell, J.E., Jr. (1996) Proc Natl Acad Sci USA 93, 7673–7678

    Article  PubMed  CAS  Google Scholar 

  65. Chin, Y.E., Kitagawa, M., Su, W.C., You, Z.H., Iwamoto, Y. and Fu, X.Y. (1996) Science 272, 719–722

    Article  PubMed  CAS  Google Scholar 

  66. Lee, C.K., Smith, E., Gimeno, R., Gertner, R. and Levy, D.E. (2000) J Immunol 164, 1286–1292

    PubMed  CAS  Google Scholar 

  67. Ouchi, T., Lee, S.W., Ouchi, M., Aaronson, S.A. and Horvath, C.M. (2000) Proc Natl Acad Sci USA 97, 5208–5213

    Article  PubMed  CAS  Google Scholar 

  68. Kumar, A., Commane, M., Flickinger, T.W., Horvath, C.M. and Stark, G.R. (1997) Science 278, 1630–1632

    Article  PubMed  CAS  Google Scholar 

  69. Fulda, S. and Debatin, K.M. (2002) Oncogene 21, 2295–2308

    Article  PubMed  CAS  Google Scholar 

  70. Dupuis, S., Dargemont, C., Fieschi, C., Thomassin, N., Rosenzweig, S., Harris, J., Holland, S.M., Schreiber, R.D. and Casanova, J.L. (200 1) Science 293, 300–303

    Google Scholar 

  71. Dupuis, S., Jouanguy, E., Al-Hajjar, S., Fieschi, C., Al-Mohsen, I.Z., Al-Jumaah, S., Yang, K., Chapgier, A., Eidenschenk, C., Eid, P., Ghonaium, A.A., Tufenkeji, H., Frayha, H., Al-Gazlan, S., Al-Rayes, H., Schreiber, R.D., Gresser, I. and Casanova, J.L. (2003) Nat Genet 3, 388–391

    Article  Google Scholar 

  72. Silver, D.L. and Montell, D.J. (2001) Cell 107, 831–841

    Article  PubMed  CAS  Google Scholar 

  73. Yamashita, S., Miyagi, C., Carmany-Rampey, A., Shimizu, T., Fujii, R., Schier, A.F. and Hirano, T. (2002) Dev Cell 2, 363–375

    Article  PubMed  CAS  Google Scholar 

  74. Darnell, J.E., Jr. (2002) Nat Rev Can 2, 740–749

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Technical University of Munich, 81675, Munich, Germany

    Tobias Dechow

  2. Memorial Sloan Kettering Cancer Center, New York, NY, 10021, USA

    Jacqueline Bromberg

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  1. Tobias Dechow
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Editors and Affiliations

  1. New York University School of Medicine, USA

    Pravin B. Sehgal  & David E. Levy  & 

  2. Osaka University, Japan

    Toshio Hirano

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Dechow, T., Bromberg, J. (2003). Constitutively Active STATs and Cellular Transformation. In: Sehgal, P.B., Levy, D.E., Hirano, T. (eds) Signal Transducers and Activators of Transcription (STATs). Springer, Dordrecht. https://doi.org/10.1007/978-94-017-3000-6_40

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  • DOI: https://doi.org/10.1007/978-94-017-3000-6_40

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