Mutations which abolish phosphorylation of the TRAF-binding domain of TNF receptor 2 enhance receptor-mediated NF-kappa B activation
| Autor: | Patrick W. P. Ng, Alan G. Porter, Reiner U. Jänicke |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
EGF-like domain
Molecular Sequence Data Biophysics Gene Expression Protein Serine-Threonine Kinases Biochemistry Peptide Mapping Receptors Tumor Necrosis Factor Phosphorylation cascade Serine HAMP domain Antigens CD Genes Reporter Receptors Tumor Necrosis Factor Type II Protein phosphorylation Amino Acid Sequence Phosphorylation Molecular Biology Binding Sites Kinase Chemistry NF-kappa B Cell Biology Molecular biology Recombinant Proteins Mutation Binding domain Signal Transduction |
| Zdroj: | Biochemical and biophysical research communications. 244(3) |
| ISSN: | 0006-291X |
| Popis: | We demonstrate that a 41 amino acid region (amino acids 379 to 419) in the cytoplasmic domain of tumor necrosis factor receptor 2 (TNFR2) is phosphorylated by unidentified kinase(s) both in vitro and in vivo. This domain (denoted x1c) corresponds almost exactly to the previously identified TRAF-binding domain and is by itself sufficient as a substrate for phosphorylation. In addition, the x1c domain is also crucial for TNFR2-mediated NF-kappa B activation. The cytoplasmic domain of TNFR2 lacks tyrosines, and conversion of all 12 potential serine and threonine phosphorylation targets in x1c to alanines either had no effect on NF-kappa B activation or resulted in enhanced NF-kappa B activity, depending on the structural context of x1c. The results show that while the TRAF-binding domain of TNFR2 is a major target of kinases, its phosphorylation is not required for NF-kappa B activation. Our data moreover suggest that phosphorylation of x1c negatively regulates the activation of NF-kappa B. |
| Databáze: | OpenAIRE |
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