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A single tyrosine of the interleukin-9 (IL-9) receptor is required for STAT activation, antiapoptotic activity, and growth regulation by IL-9.

Interleukin-9 (IL-9), a T-cell-derived cytokine, interacts with a specific receptor associated with the IL-2 receptor gamma chain. In this report, we analyze the functional domains of the human IL-9 receptor transfected into mouse lymphoid cell lines. Three different functions were examined: growth stimulation in factor-dependent pro-B Ba/F3 cells, protection against dexamethasone-induced apoptosis, and Ly-6A2 induction in BW5147 lymphoma cells. The results indicated that a single tyrosine, at position 116 in the cytoplasmic domain, was required for all three activities. In addition, we observed that human IL-9 reduced the proliferation rate of transfected BW5147 cells, an effect also dependent on the same tyrosine. This amino acid was necessary for IL-9-mediated tyrosine phosphorylation of the receptor and for STAT activation but not for IRS-2/4PS activation or for JAK1 phosphorylation, which depended on a domain closer to the plasma membrane. We also showed that JAK1 was constitutively associated with the IL-9 receptor. Activated STAT complexes induced by IL-9 were found to contain STAT1, STAT3, and STAT5 transcription factors. Moreover, sequence homologies between human IL-9 receptor tyrosine 116 and tyrosines (of other receptors activating STAT3 and STAT5 were observed. Taken together, these data indicate that a single tyrosine of the IL-9 receptor, required for activation of three different STAT proteins, is necessary for distinct activities of this cytokine, including proliferative responses.

Pubmed ID: 8756628

Authors

  • Demoulin JB
  • Uyttenhove C
  • Van Roost E
  • DeLestrĂ© B
  • Donckers D
  • Van Snick J
  • Renauld JC

Journal

Molecular and cellular biology

Publication Data

September 26, 1996

Associated Grants

None

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Ly
  • Apoptosis
  • Base Sequence
  • Cell Division
  • DNA-Binding Proteins
  • Humans
  • Interleukin-9
  • Janus Kinase 1
  • Janus Kinase 3
  • Lymphoma
  • Mast-Cell Sarcoma
  • Mice
  • Milk Proteins
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Protein-Tyrosine Kinases
  • Receptors, Erythropoietin
  • Receptors, Interleukin
  • Receptors, Interleukin-2
  • Receptors, Interleukin-9
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT3 Transcription Factor
  • STAT5 Transcription Factor
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Structure-Activity Relationship
  • Trans-Activators
  • Transfection
  • Tumor Cells, Cultured
  • Tyrosine