MADD, a Novel Death Domain Protein That Interacts with the Type 1 Tumor Necrosis Factor Receptor and Activates Mitogen-activated Protein Kinase
| Autor: | Andrea R. Schievella, Lih-Ling Lin, James Graham, Jennifer Chen |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Male
MAPK/ERK pathway Death Domain Receptor Signaling Adaptor Proteins Transcription Genetic Molecular Sequence Data Saccharomyces cerevisiae Mitogen-activated protein kinase kinase Polymerase Chain Reaction Biochemistry Receptors Tumor Necrosis Factor Cell Line Phospholipase A2 Antigens CD Guanine Nucleotide Exchange Factors Humans Point Mutation Amino Acid Sequence RNA Messenger Cloning Molecular Molecular Biology Conserved Sequence DNA Primers Death domain Binding Sites Sequence Homology Amino Acid biology MAP kinase kinase kinase Kinase Chemistry Proteins Cell Biology respiratory system TNF Receptor-Associated Factor 1 Recombinant Proteins Enzyme Activation Organ Specificity Receptors Tumor Necrosis Factor Type I Mitogen-activated protein kinase Calcium-Calmodulin-Dependent Protein Kinases Mutagenesis Site-Directed biology.protein Cancer research Phosphorylation Female Carrier Proteins |
| Zdroj: | Journal of Biological Chemistry. 272:12069-12075 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.272.18.12069 |
| Popis: | The death domain of the type 1 tumor necrosis factor receptor (TNFR1) mediates interactions with several proteins involved in signaling the downstream effects of TNF. We have used the yeast interaction trap to isolate a protein, MADD, that associates with the death domain of TNFR1 through its own C-terminal death domain. MADD interacts with TNFR1 residues that are critical for signal generation and coimmunoprecipitates with TNFR1, implicating MADD as a component of the TNFR1 signaling complex. Importantly, we have found that overexpression of MADD activates the mitogen-activated protein (MAP) kinase extracellular signal-regulated kinase (ERK), and expression of the MADD death domain stimulates both the ERK and c-JUN N-terminal kinase MAP kinases and induces the phosphorylation of cytosolic phospholipase A2. These data indicate that MADD links TNFR1 with MAP kinase activation and arachidonic acid release and provide further insight into the mechanisms by which TNF exerts its pleiotropic effects. |
| Databáze: | OpenAIRE |
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