TAK1–TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-κB signaling pathways
Copyright policy )TAK1–TAB1 fusion protein: a novel constitutively active mitogen-activated protein kinase kinase kinase that stimulates AP-1 and NF-κB signaling pathways
TAK1 mitogen-activated protein kinase kinase kinase (MAP3K) is activated by its specific activator, TAK1-binding protein 1 (TAB1). A constitutively active TAK1 mutant has not yet been generated due to the indispensable requirement of TAB1 for TAK1 kinase activity. In this study, we generated a novel constitutively active TAK1 by fusing its kinase domain to the minimal TAK1-activation domain of TAB1. Co-immunoprecipitation assay demonstrated that these domains interacted intra-molecularly. The TAK1-TAB1 fusion protein showed a significant MAP3K activity in vitro and activated c-Jun N-terminal kinase/p38 MAPKs and IkappaB kinase in vivo, which was followed by increased production of interleukin-6. These results indicate that the fusion protein is useful for characterizing the physiological roles of the TAK1-TAB1 complex.
- University of Toyama Japan
Binding Sites, DNA, Complementary, Models, Genetic, Interleukin-6, MAP Kinase Signaling System, Blotting, Western, Interleukin-8, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Enzyme-Linked Immunosorbent Assay, MAP Kinase Kinase Kinases, Precipitin Tests, Mutation, Humans, Mitogen-Activated Protein Kinases, Carrier Proteins, Adaptor Proteins, Signal Transducing, HeLa Cells, Protein Binding
Binding Sites, DNA, Complementary, Models, Genetic, Interleukin-6, MAP Kinase Signaling System, Blotting, Western, Interleukin-8, Intracellular Signaling Peptides and Proteins, JNK Mitogen-Activated Protein Kinases, NF-kappa B, Enzyme-Linked Immunosorbent Assay, MAP Kinase Kinase Kinases, Precipitin Tests, Mutation, Humans, Mitogen-Activated Protein Kinases, Carrier Proteins, Adaptor Proteins, Signal Transducing, HeLa Cells, Protein Binding
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