Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Kozma, N; Halasz, M; Polgar, B; Poehlmann, TG; Markert, UR; Palkovics, T; Keszei, M; Par, G; Kiss, K; Szeberenyi, J; Grama, L; Szekeres-Bartho, J.
Progesterone-induced blocking factor activates STAT6 via binding to a novel IL-4 receptor.
J Immunol. 2006; 176(2): 819-826.
Doi: 10.4049/jimmunol.176.2.819
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- Führende Autor*innen der Med Uni Graz
- Kozma Noemi
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- Abstract:
- Progesterone-induced blocking factor (PIBF) induces Th2-dominant cytokine production. Western blotting and EMSA revealed phosphorylation as well as nuclear translocation of STAT6 and inhibition of STAT4 phosphorylation in PIBF-treated cells. The silencing of STAT6 by small interfering RNA reduced the cytokine effects. Because the activation of the STAT6 pathway depends on the ligation of IL-4R, we tested the involvement of IL-4R in PIBF-induced STAT6 activation. Although PIBF does not bind to IL-4R, the blocking of the latter with an Ab abolished PIBF-induced STAT6 activation, whereas the blocking of the IL-13R had no effect. PIBF activated suppressor of cytokine signaling-3 and inhibited IL-12-induced suppressor of cytokine signaling-1 activation. The blocking of IL-4R counteracted all the described effects, suggesting that the PIBF receptor interacts with IL-4R alpha-chain, allowing PIBF to activate the STAT6 pathway. PIBF did not phosphorylate Jak3, suggesting that the gamma-chain is not needed for PIBF signaling. Confocal microscopic analysis revealed a colocalization and at 37 degrees C a cocapping of the FITC PIBF-activated PIBF receptor and PE anti-IL-4R-labeled IL-4R. After the digestion of the cells with phosphatidylinositol-specific phospholipase C, the STAT6-activating effect of PIBF was lost, whereas that of IL-4 remained unaltered. These data suggest the existence of a novel type of IL-4R composed of the IL-4R alpha-chain and the GPI-anchored PIBF receptor.
- Find related publications in this database (using NLM MeSH Indexing)
- Base Sequence -
- Cytokines - biosynthesis
- Humans -
- Lymphocytes - drug effects Lymphocytes - immunology Lymphocytes - metabolism
- Membrane Glycoproteins - metabolism
- Pregnancy Proteins - metabolism Pregnancy Proteins - pharmacology
- Protein Binding -
- RNA Interference -
- RNA, Small Interfering - genetics
- Receptors, Interleukin-4 - metabolism
- Recombinant Proteins - pharmacology
- STAT6 Transcription Factor - genetics STAT6 Transcription Factor - metabolism
- Signal Transduction -
- Suppressor Factors, Immunologic -