Signal transduction pathway of interleukin-4 and interleukin-13 in human B cells derived from X-linked severe combined immunodeficiency patients

Kenji Izuhara, Toshio Heike, Takeshi Otsuka, Kunihiro Yamaoka, Mitsuhumi Mayumi, Takashi Imamura, Yoshiyuki Niho, Nobuyuki Harada

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Interleukin-4 (IL-4) and IL-13 are functionally similar cytokines. The functional IL-4 receptor (IL-4R) consists of the IL-4Rα chain (IL-4Rα) and the IL-2Rγ chain (γ(c)), which is shared by the IL-2, IL-7, IL-9, and IL- 15 receptors. The functional IL-13R is thought to involve the IL-4Rα but not γ(c). In this study, we have analyzed activation of members of the Janus tyrosine kinase (Jak) family and signal transducers and activators of transcription (STAT) 6 induced by IL-4 and IL-13 in Epstein-Barr virus- transformed B cells derived from two patients of X-linked severe combined immunodeficiency, who have mutations of the γ(c) gene in the extracellular and intracellular domains. In these B cells, IL-4 failed to induce tyrosine phosphorylation of Jak3 and activation of STAT6, or activation of these molecules was significantly decreased compared with Epstein-Barr virus- transformed normal B cells. In contrast, IL-13 activated STAT6 in these cells as well as normal B cells. However, Jak3 was not activated by IL-13, even in normal B cells. These results clearly indicated that γ(c) is essential for activation of Jak3 and STAT6 in the signal transduction pathway of IL-4 in human B cells and that IL-13 does not utilize γ(c) but activates STAT6 through an alternative pathway, which is not impaired in B cells of X-linked severe combined immunodeficiency patients.

Original languageEnglish
Pages (from-to)619-622
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number2
DOIs
Publication statusPublished - 1996 Jan 12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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