Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/8907
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Type: Journal article
Title: A cell type-specific constitutive point mutant of the common β-subunit of the human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors requires the GM-CSF receptor α-subunit for activation
Other Titles: A cell type-specific constitutive point mutant of the common beta-subunit of the human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors requires the GM-CSF receptor alpha-subunit for activation
Author: Jenkins, B.
Le, F.
Gonda, T.
Citation: Journal of Biological Chemistry, 1999; 274(13):8669-8677
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Issue Date: 1999
ISSN: 0021-9258
1083-351X
Statement of
Responsibility: 
Brendan J. Jenkins, Fei Le, and Thomas J. Gonda
Abstract: The high affinity receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF) consists of a cytokine-specific α-subunit (hGMRα) and a common signal-transducing β-subunit (hβc) that is shared with the interleukin-3 and -5 receptors. We have previously identified a constitutively active extracellular point mutant of hβc, I374N, that can confer factor independence on murine FDC-P1 cells but not BAF-B03 or CTLL-2 cells (Jenkins, B. J., D’Andrea, R. J., and Gonda, T. J. (1995) EMBO J. 14, 4276–4287). This restricted activity suggested the involvement of cell type-specific signaling molecules in the activation of this mutant. We report here that one such molecule is the mouse GMRα (mGMRα) subunit, since introduction of mGMRα, but not hGMRα, into BAF-B03 or CTLL-2 cells expressing the I374N mutant conferred factor independence. Experiments utilizing mouse/human chimeric GMRα subunits indicated that the species specificity lies in the extracellular domain of GMRα. Importantly, the requirement for mGMRα correlated with the ability of I374N (but not wild-type hβc) to constitutively associate with mGMRα. Expression of I374N in human factor-dependent UT7 cells also led to factor-independent proliferation, with concomitant up-regulation of hGMRα surface expression. Taken together, these findings suggest a critical role for association with GMRα in the constitutive activity of I374N.
Keywords: Cell Line; Animals; Humans; Mice; Retroviridae; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Receptors, Interleukin-3; Receptors, Interleukin; Recombinant Fusion Proteins; Flow Cytometry; Cloning, Molecular; Cell Division; Gene Expression; Amino Acid Sequence; Point Mutation; Molecular Sequence Data; Receptors, Interleukin-5
RMID: 0030004913
DOI: 10.1074/jbc.274.13.8669
Appears in Collections:Medicine publications

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