Vav synergizes with protein kinase CΘ to mediate IL-4 gene expression in response to CD28 costimulation in T cells
The secretion of IL-4, which displays many important immunoregulatory functions, is restricted to cells of the Th2 subtype. In this study, we investigated the early signaling events leading to the activation of IL-4 transcription. Vav, the protein kinase C (PKC) isoform Θ, and the adaptor protein SL...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
April 1, 2000
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| In: |
The journal of immunology
Year: 2000, Volume: 164, Issue: 7, Pages: 3829-3836 |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.164.7.3829 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.164.7.3829 Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/164/7/3829 
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| Author Notes: | Steffen P. Hehner, Min Li-Weber, Marco Giaisi, Wulf Dröge, Peter H. Krammer, and M. Lienhard Schmitz |
| Summary: | The secretion of IL-4, which displays many important immunoregulatory functions, is restricted to cells of the Th2 subtype. In this study, we investigated the early signaling events leading to the activation of IL-4 transcription. Vav, the protein kinase C (PKC) isoform Θ, and the adaptor protein SLP76 (SH2-domain-containing leukocyte protein of 76 kDa), induced transcription from the IL-4 promoter. Vav and PKCΘ synergistically activated human IL-4 promoter transcription and IL-4 mRNA production and were found to be constitutively associated in vivo. CD3/CD28-induced IL-4 transcription was inhibited upon coexpression of dominant negative forms of Vav, the adaptor proteins LAT (linker for activation of T cells) and SLP76, PKCΘ, and components of the pathways leading to the activation of c-Jun N-terminal kinase (mitogen-activated protein kinase kinase 7 (MKK7), mixed lineage kinase 3 (MLK3)) and NF-κB (IκB kinase α and IκB kinase β). The Vav/PKCΘ-mediated synergistic activation of IL-4 transcription was not inhibited by cyclosporin A. Three independent experimental approaches revealed that Vav/PKCΘ-derived signals selectively target the P1 and positive regulatory element (PRE)-I elements contained within the human IL-4 promoter. Vav/PKCΘ strongly activated a luciferase reporter construct controlled by trimerized P1 or PRE-I elements and furthermore stimulated DNA binding of nuclear proteins to the P1 and PRE-I elements. Vav/PKCΘ-induced transcription from the IL-4 promoter was almost completely abrogated by mutation of either the P1 or the PRE-I element within the entire IL-4 promoter. |
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| Item Description: | Im Titel ist theta als griechischer Buchstabe dargestellt Gesehen am 03.02.2021 |
| Physical Description: | Online Resource |
| ISSN: | 1550-6606 |
| DOI: | 10.4049/jimmunol.164.7.3829 |