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

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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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Interleukin-9
Signal transduction
Cell proliferation
Signal Transduction
STAT3 Transcription Factor
Cell Proliferation
Janus Kinases
Interleukin-9 Receptors
Cell growth
Insulin Receptor Substrate Proteins
Phosphorylation
Tyrosine
Phosphotransferases
Growth
Chemical activation
human IL9R protein
Consensus Sequence
Point Mutation
Substitution reactions
Genes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Critical cytoplasmic domains of human interleukin-9 receptor α chain in interleukin-9-mediated cell proliferation and signal transduction. / Zhu, Yuan Xiao; Sun, Hui (Herb); Tsang, Monica Lik Shing; McMahel, Jon; Grigsby, Susan; Yin, Tinggui; Yang, Yu Chung.

In: Journal of Biological Chemistry, Vol. 272, No. 34, 22.08.1997, p. 21334-23140.

Research output: Contribution to journalArticle

Zhu, Yuan Xiao ; Sun, Hui (Herb) ; Tsang, Monica Lik Shing ; McMahel, Jon ; Grigsby, Susan ; Yin, Tinggui ; Yang, Yu Chung. / Critical cytoplasmic domains of human interleukin-9 receptor α chain in interleukin-9-mediated cell proliferation and signal transduction. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 34. pp. 21334-23140.
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