A Single Tyrosine of the Interleukin-9 (IL-9) Receptor Is Required for STAT Activation, Antiapoptotic Activity, and Growth Regulation by IL-9

• DOI: 10.1128/mcb.16.9.4710
• Publication Date: 2015-10-09T00:25:47Z
• Authors: Jean-Baptiste Dem...; Catherine Uyttenhove; Emiel Van Roost; Brigite de Lestré; Dominique Donckers; Jacques Van Snick; Jean-Christophe R...
• Keywords: 0301 basic medicine; Base Sequence; Lymphoma; Molecular Sequence Data; Interleukin-9; Janus Kinase 3; Mast-Cell Sarcoma; Apoptosis; Janus Kinase 1; Protein-Tyrosine Kinases; Milk Proteins; DNA-Binding Proteins; Mice; 03 medical and health sciences; Receptors, Erythropoietin; Animals; Antigens, Ly; Humans; Amino Acid Sequence; Phosphorylation; Protein Processing, Post-Translational; Cell Division

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.