Prerequisites for Functional Interleukin 31 Signaling and Its Feedback Regulation by Suppressor of Cytokine Signaling 3 (SOCS3)
| Autor: | Albert Duschl, Jutta Horejs-Hoeck, Michaela Mittermeir, Angela Schmiedlechner, Elisabeth Maier, Theresa Neuper, Stefanie Ess |
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| Rok vydání: | 2015 |
| Předmět: |
Amino Acid Motifs
Immunology Intracellular Space Suppressor of Cytokine Signaling Proteins Biology Biochemistry Suppressor of cytokine signalling Humans Protein Isoforms SOCS5 SOCS6 SOCS3 Autocrine signalling Molecular Biology SOCS2 Feedback Physiological Oncostatin M Receptor beta Subunit Suppressor of cytokine signaling 1 Interleukins Cell Membrane Oncostatin M receptor Receptors Interleukin Cell Biology Cell biology HEK293 Cells Gene Expression Regulation Suppressor of Cytokine Signaling 3 Protein Tyrosine HeLa Cells Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 290:24747-24759 |
| ISSN: | 0021-9258 |
| Popis: | Interleukin-31 (IL-31) is a T helper type 2 cell-derived cytokine tightly associated with inflammatory skin disorders. IL-31-induced signaling is mediated by a receptor complex composed of oncostatin M receptor β and the cytokine-specific receptor subunit IL-31Rα, of which there are several isoforms. The latter can be classified as long or short isoforms with respect to their intracellular domain. At present, the signaling capabilities of the different isoforms remain inchoately understood, and potential mechanisms involved in negative regulation of IL-31Rα signaling have so far not been studied in detail. Here, we show that both the long and short isoforms of IL-31Rα are capable of inducing STAT signaling. However, the presence of a functional JAK-binding box within IL-31Rα is an essential prerequisite for functional IL-31-mediated STAT3 signaling. Moreover, both the long and short isoforms require oncostatin M receptor β for their activity. We also show that IL-31 induces expression of four suppressor of cytokine signaling family members and provide evidence that SOCS3 acts as a potent feedback inhibitor of IL-31-induced signaling. Taken together, this study identifies crucial requirements for IL-31 signaling and shows its counter-regulation by SOCS3. |
| Databáze: | OpenAIRE |
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