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Roles of Jak Kinases in Human GM-CSF Receptor

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Bone Marrow Transplantation

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Abstract

The IL-3 and GM-CSF (hGMR) receptors consist of two subunits, α and β, both of which are members of the cytokine receptor superfamily. Chemical cross-linking and immunoprecipitation revealed that the α and β subunits associate following stimulation with GM-CSF, but the β subunit forms a homodimer even in the absence of the ligand. We analyzed the mechanism of c-fos mRNA activation by GM-CSF using several hGMRβ subunit mutants. In addition to boxl region, a membrane distal region (a.a. 544-589) of hGMRβ is required for c-fos activation. Only one tyrosine residue (Tyr577) exists within the region 544–589, and substitution of Tyr577 to phenylalanine in GMRβ 589 resulted in the loss of c-fos activation. In contrast, the same substitution in a wild type receptor did not affect GM-CSF-induced activities such as c-fos mRNA induction and proliferation but abolished Shc phosphorylation. These results suggest that the activation of She is not essential for c-fos activation and several tyrosine residues coordinate to activate c-fos activation.

It is well documented that IL-3 or GM-CSF activates JAK in various cells. However the role of JAK2 in IL-3/GM-CSF functions is largely unknown. We examined the role of JAK2 in GM-CSF-induced signaling pathways. Dominant negative JAK2 (∆JAK2) lacking the C-terminus kinase domain, suppressed IL3/GM-CSF induced c-fos activation, c-myc activation and proliferation, suggesting that JAK2 is involved in both signaling pathways. Several tyrosine residues are known to be phosphorylated by GM-CSF within this region and JAK2 expressed transiently in COS7 cells phosphorylated certain tyrosine residues within hGMRß. JAK2 also phosphorylated PTP1D in COS7 cells. PTP1D and Shc are phosphorylated by IL-3/GM-CSF in BA/F3 cells, but these phosphorylation events were inhibited by expression of ∆JAK2. Taken together, these results indicate that JAK2 is a primary kinase regulating all the known activities of GM-CSF. JAK2 mediates GM-CSF induced c-fos activation through receptor phosphorylation and Shc/PTP1D activation.

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References

  1. Arai, K., Lee, F., Miyajima, A.,’ Miyatake, S., Arai, N. and Yokota, T. (1990) Ann. Rev. Biochem. 59, 783–836

    Article  PubMed  CAS  Google Scholar 

  2. Miyajima, A., Kitamura, T., Harada, N., Yokota, T. and Arai, K. (1992) Ann. Rev. Immunol. 10, 295–331

    Article  CAS  Google Scholar 

  3. Miyajima, A., Mui, A. L.-F., Ogorochi, T. and Sakamaki, K. (1993) Blood 82, 1960–1974

    PubMed  CAS  Google Scholar 

  4. Watanabe, S., Muto, A., Yokota, T., Miyajima, A. and Arai, K. (1993) Mol. Biol. Cell 4, 983–992

    PubMed  CAS  Google Scholar 

  5. Watanabe, S., Ito, Y., Miyajima, A. and Arai, K. (1995) J. Biol. Chem. 270, 9615–9621

    Article  PubMed  CAS  Google Scholar 

  6. Watanabe, S., Ishida, S., Koike, K. and Arai, K. (1995) Mol. Biol. Cell 6, 627–636

    PubMed  CAS  Google Scholar 

  7. Ihle, J. N., Witthuhn, B. A., Quelle, F. W., Yamamoto, K., Thierfelder, W. E., Kreider, B. and Silvennoinen, O. (1994) TIBS 19, 222–227

    Google Scholar 

  8. Luo, II., Hanratty, W. P. and Dearolf, C. R. (1995) EMBO J. 14, 1412–1420

    Google Scholar 

  9. Darnell Jr., J. E., Kerr, I. M. and Stark, G. R. (1994) Science 264, 1415–1421

    Article  PubMed  CAS  Google Scholar 

  10. Muller, M., Briscoe, J., Laxton, C., Guschin, D., Ziemiecki, A., Silvennoinen, O., Harpur, A. G., Barbieri, G., Witthuhn, B. A., Schindler, C., Pellegrini, S., Wilks, A. F., Ihle, J. N., Stark, G. R. and Kerr, I. M. (1993) Nature 366, 129–135

    Article  PubMed  CAS  Google Scholar 

  11. Watling, D., Guschin, D., Muller, M., Silvennoinen, O., Witthuhn, B. A., Quelle, F. W., Rogers, N. C., Schindler, C., Stark, G. R. and Ihle, J. N. (1993) Nature 366, 166–170

    Article  PubMed  CAS  Google Scholar 

  12. Velazquez, L., Fellous, M., Stark, G. R. and Pellegrini, S. (1992) Cell 70, 313–322

    Article  PubMed  CAS  Google Scholar 

  13. Wegenka, U. M., Lutticken, C., Buschmann, J., Yuan, J., Lottspeich, F., Muller-Esterl, W., Schindler, C., Roeb, E., Heinrich, P. C. and Horn, F. (1994) Mol. Cell. Biol. 14, 3186–3196

    PubMed  CAS  Google Scholar 

  14. Wakao, H., Gouilleux, F. and Groner, B. (1994) EMBO J. 13, 2182–2191

    Google Scholar 

  15. Silvennoinen, O., Witthuhn, B. A., Quelle, F. W., Cleveland, J. L., Yi, T. and Ihle, J. N. (1993) Proc. Natl. Acad. Sci. USA 90, 8429–8433

    Article  PubMed  CAS  Google Scholar 

  16. Quelle, F. W., Sato, N., Witthuhn, B. A., Inhorn, R. C., Eder, M.,Miyajima, A., Griffin, J. and Ihle, J. N. (1994) Mol. Cell. Biol. 14, 4335–4341

    PubMed  CAS  Google Scholar 

  17. Taniguchi, T. (1995) Science 268, 251–255

    Article  PubMed  CAS  Google Scholar 

  18. Brizzi, M. F., Zini, M. G., Aronica, M. G., Blechman, J. M., Yarden, Y. and Pegoraro, L. (1994) J. Biol. Chem. 269, 31680–31684

    PubMed  CAS  Google Scholar 

  19. Nishinakamura, R., Nakayama, N., Hirabayashi, Y., Inoue, T., Aud, D., McNeil, T., Azuma, S., Yoshida, S., Toyoda, Y., Arai, K., Miyajima, A. and Murray, R. (1995) Immunity 2, 211–222

    Article  PubMed  CAS  Google Scholar 

  20. Dranoff, G., Grawford, A. D., Sadelain, M., Ream, B., Rashid, A., Bronson, R. T., Dickersin, G. R., Bachurski, C. J., Mark, E. L., Whitsett, J. A. and Mulligan, R. C. (1994) Science 264, 713–716

    Article  PubMed  CAS  Google Scholar 

  21. Watanabe, S., Mui, A. L.-F., Muto, A., Chen, J. X., Hayashida, K., Miyajima, A. and Arai, K. (1993) Mol. Cell. Biol. 13, 1440–1448

    PubMed  CAS  Google Scholar 

  22. Nishijima, I., Nakahata, T., Hirabayashi, Y., Inoue, T., Kurata, H., Miyajima, A., Hayashi, N., Iwakura, Y., Arai, K. and Yokota, T. (1995) Mol. Biol. Cell 6, 497–508

    PubMed  CAS  Google Scholar 

  23. Pelicci, G., Lanfrancone, L., Grignani, F., McGlade, J., Cavallo, F., Forni, G., Nicoletti, I., Grignani, F., Pawson, T. and Pelicci, P. G. (1992) Cell 70,93–104

    Article  PubMed  CAS  Google Scholar 

  24. Vogel, W., Lammers, R., Huang, J. and Ullrich, A. (1993) Science 259, 1611–1614

    Article  PubMed  CAS  Google Scholar 

  25. Welham, M. J., Dechert, U., Leslie, K. B., Jirik, F. and Schrader, J. W. (1994) J. Biol. Chem. 269, 23764–23768

    PubMed  CAS  Google Scholar 

  26. Li, W., Nishimura, R., Kashishian, A., Batzer, A. G., Kim, W. J. 1-L, Cooper, J. A. and Schlessinger, J. (1994) Mol. Cell. Biol. 14, 509–517

    Article  PubMed  CAS  Google Scholar 

  27. Kaziro, Y., Itoh, H, Kozasa, T., Nakafuku, M. and Satoh, T. (1991) Annu. Rev. Biochem. 60, 349–400

    Article  PubMed  CAS  Google Scholar 

  28. Torigoe, T., O’Connor, R., Santoli, D. and Reed, J. C. (1992) Blood 80, 617–624

    PubMed  CAS  Google Scholar 

  29. Fu, X.-Y. and Zhang, J.-J. (1993) Cell 74, 1135–1145

    Article  PubMed  CAS  Google Scholar 

  30. Fukumoto, Y., Kaibuchi, K., Oku, N., Hori, Y. and Takai, Y. (1990) J. Biol. Chem. 265, 774–780

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular and Developmental Biology, University of Tokyo, 4-6-1, Shirokane-dai, Minato-ku, Tokyo 108, Japan

    Sumiko Watanabe, Akihiko Muto, Tohru Itoh & Ken-ichi Arai

  2. Department of Clinical Oncology, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokane-dai, Minato-ku, Tokyo 108, Japan

    Tatsutoshi Nakahata

Authors
  1. Sumiko Watanabe
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  2. Akihiko Muto
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  3. Tohru Itoh
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  4. Tatsutoshi Nakahata
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  5. Ken-ichi Arai
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Editor information

Editors and Affiliations

  1. First Department of Pathology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570, Japan

    Susumu Ikehara M.D., Ph.D. (Professor) (Professor)

  2. International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162, Japan

    Fumimaro Takaku M.D., Ph.D. (President) (President)

  3. Department of Pediatrics, All Children’s Hospital, University of South Florida, 801 Sixth Street South, Box 753, St. Petersburg, FL, 33701, USA

    Robert A. Good M.D., Ph.D., D.Sc., FACP (Distinguished Research Professor, University of South Florida, Head of Allergy and Clinical Immunology) (Distinguished Research Professor, University of South Florida, Head of Allergy and Clinical Immunology)

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© 1996 Springer-Verlag Tokyo

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Watanabe, S., Muto, A., Itoh, T., Nakahata, T., Arai, Ki. (1996). Roles of Jak Kinases in Human GM-CSF Receptor. In: Ikehara, S., Takaku, F., Good, R.A. (eds) Bone Marrow Transplantation. Springer, Tokyo. https://doi.org/10.1007/978-4-431-68320-9_14

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  • DOI: https://doi.org/10.1007/978-4-431-68320-9_14

  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-68322-3

  • Online ISBN: 978-4-431-68320-9

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