Molecular analysis of human interleukin-9 receptor transcripts in peripheral blood mononuclear cells - Identification of a splice variant encoding for a nonfunctional cell surface receptor

Grasso, L;Huang, MX;Sullivan, CD;Messler, CJ;Nicolaides, NC;et.al.
(1998) Journal of Biological Chemistry — Vol. 273, n° 37, p. 24016-24024 (1998)

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Authors
  • Grasso, L
    Author
  • Huang, MX
    Author
  • Sullivan, CD
    Author
  • Messler, CJ
    Author
  • Renauld, Jean-Christopheorcid-logoUCLouvain
    Author
  • Nicolaides, NC
    Author
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Abstract
Genetic studies on mouse models of asthma have identified interleukin-9 (IL9) as a determining factor in controlling bronchial hyperresponsiveness, a hallmark of the disease. Recently, the human IL9 receptor (hIL9R) gene locus has also been implicated in determining susceptibility to bronchial hyperresponsiveness and asthma. in order to evaluate the structure and function of the encoded product, we analyzed receptor transcripts derived from peripheral blood mononuclear cells of 50 unrelated donors. Sequence analysis of time entire coding region identified a splice variant that contains an in frame deletion of a single residue at codon 173 (Delta Q). This variant could be permanently expressed in a cytokine-dependent murine T-cell line but lacked the ability to induce proliferation in response to human IL9. In situ analyses of cells expressing the wild-type and Delta Q receptors found both forms to be expressed at the cell surface, but the Delta Q receptor was unable to bind hIL9 and could not be recognized by N-terminal specific antibodies. These findings demonstrate that hIL9R Delta Q presents an altered structure and function and suggests its potential role in down-regulating IL9 signaling in effector cells and associated biological processes.
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Grasso, L., Huang, M., Sullivan, C., Messler, C., Kiser, M., Dragwa, C., Holroyd, K., Renauld, J.-C., Levitt, R., & Nicolaides, N. (1998). Molecular analysis of human interleukin-9 receptor transcripts in peripheral blood mononuclear cells - Identification of a splice variant encoding for a nonfunctional cell surface receptor. Journal of Biological Chemistry, 273(37), 24016-24024. https://doi.org/10.1074/jbc.273.37.24016 (Original work published 1998)