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Tyrosine kinase activation through the extracellular domains of cytokine receptors

Nature volume 362, pages 646648 (15 April 1993) | Download Citation

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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.

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Affiliations

  1. Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), 3-1 Koyadai, Tsukuba, Ibaraki 305, Japan

    • Tomoki Chiba
    • , Yuka Nagata
    • , Mitsuru Machide
    • , Atsushi Kishi
    • , Hiroshi Amanuma
    • , Masahide Sugiyama
    •  & Kazuo Todokoro

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https://doi.org/10.1038/362646a0

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