Interleukin-9 Induces Tyrosine Phosphorylation of Insulin Receptor Substrate-1 via JAK Tyrosine Kinases
| Autor: | Gustav E. Lienhard, James N. Ihle, Frederick W. Quelle, Tinggui Yin, Susanne R. Keller, Monica Lik-Shing Tsang, Bruce A. Witthuhn, Yu-Chung Yang |
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| Rok vydání: | 1995 |
| Předmět: |
T-Lymphocytes
Protein tyrosine phosphatase Transfection SH2 domain Biochemistry Receptor tyrosine kinase Cell Line Mice chemistry.chemical_compound Proto-Oncogene Proteins Chlorocebus aethiops Animals Phosphorylation Phosphotyrosine Molecular Biology TYK2 Kinase biology Interleukin-9 Janus Kinase 3 Proteins JAK-STAT signaling pathway Tyrosine phosphorylation Janus Kinase 1 Cell Biology Janus Kinase 2 Protein-Tyrosine Kinases Phosphoproteins Recombinant Proteins Cell biology Kinetics chemistry ROR1 Insulin Receptor Substrate Proteins biology.protein Tyrosine Interleukin-4 Tyrosine kinase |
| Zdroj: | Journal of Biological Chemistry. 270:20497-20502 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.270.35.20497 |
| Popis: | Interleukin (IL)-9 stimulates the proliferation of a variety of hematopoietic lineages through its interaction with a receptor of the cytokine receptor superfamily. In the studies presented here, we have begun to characterize the downstream signaling pathways activated by IL-9. In addition to the activation of JAK1 and JAK3 tyrosine kinases, IL-9, unlike most hematopoietic cytokines but similar to IL-4, induces the tyrosine phosphorylation of a 170-kDa protein that is related to the insulin receptor substrate-1 (IRS-1). We further demonstrate for the first time that IRS-1 is not only associated with JAK1 but also tyrosine phosphorylated and functionally involved in IL-9 signaling in TS1 lymphocytes transfected with the murine IRS-1 cDNA. Cotransfection studies and in vitro experiments directly demonstrate that JAK1, JAK2, or JAK3 is capable of tyrosine phosphorylating IRS-1, suggesting a functional role for these kinases in vivo. Lastly, we demonstrate that IL-9 induces the tyrosine phosphorylation of Stat3 and in this regard differs from IL-4, which triggers tyrosine phosphorylation of Stat6. Taken together, these results strongly suggest that IL-9 and IL-4 utilize common and unique signaling pathways via inducing the similar and distinct tyrosine-phosphorylated proteins. |
| Databáze: | OpenAIRE |
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