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

Luigi Grasso, Minxue Huang, Christine D. Sullivan, Carol J. Messler, Matt B. Kiser, Carl R. Dragwa, Kenneth J. Holroyd, Jean Christophe Renauld, Roy C. Levitt, Nicholas C. Nicolaides

Research output: Contribution to journalArticle

22 Scopus citations

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 the entire coding region identified a splice variant that contains an in frame deletion of a single residue at codon 173 (ΔQ). 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 ΔQ receptors found both forms to be expressed at the cell surface, but the ΔQ receptor was unable to bind hIL9 and could not be recognized by N-terminal specific antibodies. These findings demonstrate that hIL9RΔQ presents an altered structure and function and suggests its potential role in down-regulating IL9 signaling in effector cells and associated biological processes.

Original languageEnglish (US)
Pages (from-to)24016-24024
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number37
DOIs
StatePublished - Sep 11 1998
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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