Analysis of signals and functions of the chimeric human granulocyte- macrophage colony-stimulating factor receptor in BA/F3 cells and transgenic mice

Sumiko Watanabe, Yutaka Aoki, Ichiko Nishijima, Ming Jiang Xu, Ken Ichi Arai

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Receptors for GM-CSF, IL-3, and IL-5 are composed of two subunits: α, which is specific for each cytokine, and βc, which is shared by all. Although the role of βc in signal transduction has been extensively studied, the role of the α subunit has remained to be clarified. To analyze the role of the human (h) GM-CSF receptor α subunit, we constructed a chimeric receptor subunit composed of extracellular and transmembrane regions of α fused with the cytoplasmic region of βc, designated α/β. In BA/F3 cells, chimeric receptor composed of α/β,β can transduce signals for mitogen- activated protein kinase cascade activation and proliferation in response to hGM-CSF. Although phosphorylation of Jak1 but not of Jak2 occurred with stimulation of hGM-CSF, the dominant-negative Jak2 but not the dominant- negative Jak1 suppresses c-fos promoter activation. To determine whether the chimeric receptor α/β,β is functional in vivo, we developed transgenic mice expressing the chimeric receptor α/β,β. Bone marrow cells from the transgenic mice expressing the α/β,β receptor form not only GM colonies but also various lineages of colonies in response to GM-CSF. In addition, mast cells were produced when bone marrow cells of the transgenic mouse were cultured with hGM-CSF. Thus, it appears that the cytoplasmic region of the α subunit is not required for hGM-CSF promoting activities, even in bone marrow cells.

Original languageEnglish (US)
Pages (from-to)3635-3644
Number of pages10
JournalJournal of Immunology
Volume164
Issue number7
StatePublished - Apr 1 2000
Externally publishedYes

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Granulocyte-Macrophage Colony-Stimulating Factor Receptors
Bone Marrow Cells
Transgenic Mice
Interleukin-3
Interleukin-5
Granulocyte-Macrophage Colony-Stimulating Factor
Mitogen-Activated Protein Kinases
Mast Cells
Signal Transduction
Phosphorylation
Cytokines

ASJC Scopus subject areas

  • Immunology

Cite this

Analysis of signals and functions of the chimeric human granulocyte- macrophage colony-stimulating factor receptor in BA/F3 cells and transgenic mice. / Watanabe, Sumiko; Aoki, Yutaka; Nishijima, Ichiko; Xu, Ming Jiang; Arai, Ken Ichi.

In: Journal of Immunology, Vol. 164, No. 7, 01.04.2000, p. 3635-3644.

Research output: Contribution to journalArticle

Watanabe, Sumiko ; Aoki, Yutaka ; Nishijima, Ichiko ; Xu, Ming Jiang ; Arai, Ken Ichi. / Analysis of signals and functions of the chimeric human granulocyte- macrophage colony-stimulating factor receptor in BA/F3 cells and transgenic mice. In: Journal of Immunology. 2000 ; Vol. 164, No. 7. pp. 3635-3644.
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