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 RIS Download
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