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 Scopus citations

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
DOIs
StatePublished - Apr 1 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Analysis of signals and functions of the chimeric human granulocyte- macrophage colony-stimulating factor receptor in BA/F3 cells and transgenic mice'. Together they form a unique fingerprint.

  • Cite this