Abstract
INTERACTION of cytokines with their membrane receptors induces the proliferation and differentiation of a specific lineage of haematopoietic progenitors1. The molecular mechanism of cytokine receptor-mediated signal transduction is unclear because these receptors do not have tyrosine kinase activity1,2. Interleukin-3 and erythropoietin, however, induce transient tyrosine phosphorylation of a common set of proteins as a growth signal3–6, and interleukin-2 induces phosphorylation of an overlapping but distinct set of proteins6–8. Here we show that chimaeric receptors consisting of the extracellular domains of the erythropoietin receptor and the cytoplasmic domains of the interleukin-2 (or interleukin-3) receptor induce an erythropoietin-dependent tyrosine phosphorylation in interleukin-3-dependent Ba/F3 cells; however, chimaeric receptors composed of the extracellular domains of the interleukin-2 receptor and the cytoplasmic domains of the erythropoietin (or interleukin-3) receptor apparently transmit an interleukin-2-dependent signal. Our results indicate that these cytokines transmit distinct signals for activation of specific tyrosine kinases through the extracellular rather than cytoplasmic domains of the receptors.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Arai, K. et al. A. Rev Biochem. 59, 783–836 (1990).
Miyajima, A., Kitamura, T., Harada, N., Yokota, T. & Arai, K. A. Rev. Immun. 10, 295–331 (1991).
Kuramochi, S., Chiba, T., Amanuma, H., Tojo, A. & Todokoro, K. Biochem. biophys. Res. Commun. 181, 1103–1109 (1991).
Quelle, F. W. & Wojchowski, D. M. J. biol. Chem. 266, 609–614 (1991).
Isfort, R., Huhn, R. D., Frackelton, A. R. & Ihle, J. N. J. biol. Chem 263, 19203–19209 (1988).
Morla, A. O., Schreurs, J., Miyajima, A. & Wang, J. Y. J. Molec. cell. Biol. 8, 2214–2218 (1988).
Sabe, H. et al. Intl. Immun. 3, 1137–1148 (1991).
Saltzman, E. M., Luhowskyj, S. M. & Casnellie, J. E. J. biol. Chem. 264, 19979–19983 (1989).
Palacios, R. & Steinmetz, M. Cell 41, 727–734 (1985).
Todokoro, K., Kanazawa, S., Amanuma, H. & Ikawa, Y. Proc. natn. Acad. Sci. U.S.A. 84, 4126–4130 (1987).
Hatakeyama, M. et al. Science 244, 551–556 (1989).
Otani, H. et al. Proc. natn. Acad Sci. U.S.A. 89, 2789–2793 (1992).
Kuramochi, S., Ikawa, Y. & Todokoro, K. J. molec Biol. 216, 567–575 (1990).
Itoh, N. et al. Science 247, 324–327 (1990).
Kitamura, T. et al. Proc. natn. Acad Sci. U.S.A. 88, 5082–5086 (1991).
Chiba, T., Amanuma, H. & Todokoro, K. Biochem. biophys. Res. Commun. 184, 485–490 (1992).
O'Farrell, P. H. J. biol Chem. 250, 4007–4021 (1975).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Chiba, T., Nagata, Y., Machide, M. et al. Tyrosine kinase activation through the extracellular domains of cytokine receptors. Nature 362, 646–648 (1993). https://doi.org/10.1038/362646a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/362646a0
This article is cited by
-
IL-1β regulates rat mesangial cyclooxygenase II gene expression by tyrosine phosphorylation
Kidney International (1995)
-
Cyclosporin A, FK506 and dithranol alter tyrosine-specific protein phosphorylation in HaCaT keratinocytes
Archives of Dermatological Research (1995)
-
Regulation of NMDA receptors by tyrosine kinases and phosphatases
Nature (1994)
-
Second subunit of Epo receptor?
Nature (1994)
-
Cytoplasmic domains of the interleukin-2 receptor β and γ chains mediate the signal for T-cell proliferation
Nature (1994)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.