Critical cytoplasmic domains of human interleukin-9 receptor α chain in interleukin-9-mediated cell proliferation and signal transduction

Yuan Xiao Zhu, Hui Bin Sun, Monica Lik Shing Tsang, Jon McMahel, Susan Grigsby, Tinggui Yin, Yu Chung Yang

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Interleukin-9 receptor (IL-9R) complex consists of a ligand-specific α chain and IL-2R γ chain. In this study, two regions in the cytoplasmic domain of human IL-9Rα were found to be important for IL-9-mediated cell growth. A membrane-proximal region that contains the BOX1 consensus sequence is required for IL-9-induced cell proliferation and tyrosine phosphorylation of Janus kinases (JAKs). Deletion of this region or internal deletion of the BOX1 motif abrogated IL-9-induced cell proliferation and signal transduction. However, substitution of the Pro-X-Pro in the BOX1 motif with Ala-X-Ala failed to abolish IL-9-induced cell proliferation but decreased IL-9-mediated tyrosine phosphorylation of JAK kinases, insulin receptor substrate-2, and signal transducer and activator of transcription 3 (STAT3) and expression of c-myc and junB. Another important region is downstream of the BOX1 motif and contains a STAT3 binding motif YLPQ. Deletion of this region significantly impaired IL-9-induced cell growth, activation of JAK kinases, insulin receptor substrate-2, and STAT3 and expression of early response genes. A point mutation changing YLPQ into YLPA greatly reduced IL-9-induced activation of STAT3 and expression of c-myc but did not affect cell proliferation. These results suggest that cooperation or cross-talk of signaling molecules associated with different domains of IL-9Rα other than STAT3 is essential for IL-9-mediated cell growth.

Original languageEnglish (US)
Pages (from-to)21334-23140
Number of pages1807
JournalJournal of Biological Chemistry
Volume272
Issue number34
DOIs
StatePublished - Aug 22 1997

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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