Critical Cytoplasmic Domains of Human Interleukin-9 Receptor α Chain in Interleukin-9-mediated Cell Proliferation and Signal Transduction
| Autor: | Yu Chung Yang, Jon McMahel, Yuan Xiao Zhu, Tinggui Yin, Hui Bin Sun, Monica Lik Shing Tsang, Susan Grigsby |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
STAT3 Transcription Factor
Cytoplasm Proto-Oncogene Proteins c-jun T-Lymphocytes Genes myc Transfection Biochemistry Receptor tyrosine kinase Mice Structure-Activity Relationship chemistry.chemical_compound Cell surface receptor Animals Humans Point Mutation Phosphotyrosine Molecular Biology Cells Cultured Sequence Deletion Receptors Interleukin-9 biology Cell growth Interleukin-9 Intracellular Signaling Peptides and Proteins Janus Kinase 3 JAK-STAT signaling pathway Tyrosine phosphorylation Janus Kinase 1 Receptors Interleukin Cell Biology Protein-Tyrosine Kinases Phosphoproteins Molecular biology Recombinant Proteins DNA-Binding Proteins chemistry Insulin Receptor Substrate Proteins Trans-Activators biology.protein STAT protein Signal transduction Janus kinase Cell Division Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 272:21334-21340 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.272.34.21334 |
| Popis: | Interleukin-9 receptor (IL-9R) complex consists of a ligand-specific alpha chain and IL-2R gamma chain. In this study, two regions in the cytoplasmic domain of human IL-9Ralpha 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-9Ralpha other than STAT3 is essential for IL-9-mediated cell growth. |
| Databáze: | OpenAIRE |
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