TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway
Copyright policy )TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway
The biological response to tumor necrosis factor (TNF) involves activation of MAP kinases. Here we report a mechanism of MAP kinase activation by TNF that is mediated by the Rho GTPase family members Rac/Cdc42. This signaling pathway requires Src-dependent activation of the guanosine nucleotide exchange factor Vav, activation of Rac/Cdc42, and the engagement of the Rac/Cdc42 interaction site (CRIB motif) on mixed-lineage protein kinases (MLKs). We show that this pathway is essential for full MAP kinase activation during the response to TNF. Moreover, this MLK pathway contributes to inflammation in vivo.
- Yale University United States
- Washington University in St. Louis School of Medicine United States
- Ontario Institute for Cancer Research Canada
- University of Massachusetts Medical School United States
- Indiana University United States
Cells, MLK, TNF, Inbred C57BL, Biochemistry, mixed-lineage protein kinase, Molecular Genetics, Mice, Animals, Phosphorylation, Non-Receptor Type 1, Proto-Oncogene Proteins c-vav, cdc42 GTP-Binding Protein, Molecular Biology, Cells, Cultured, Inflammation, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Cultured, Tumor Necrosis Factor-alpha, Cell Biology, *Signal Transduction, Cellular and Molecular Physiology, Enzyme Activation, Mice, Inbred C57BL, Tyrosine, MAP kinase, Protein Tyrosine Phosphatase, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Developmental Biology, Signal Transduction
Cells, MLK, TNF, Inbred C57BL, Biochemistry, mixed-lineage protein kinase, Molecular Genetics, Mice, Animals, Phosphorylation, Non-Receptor Type 1, Proto-Oncogene Proteins c-vav, cdc42 GTP-Binding Protein, Molecular Biology, Cells, Cultured, Inflammation, Protein Tyrosine Phosphatase, Non-Receptor Type 1, Cultured, Tumor Necrosis Factor-alpha, Cell Biology, *Signal Transduction, Cellular and Molecular Physiology, Enzyme Activation, Mice, Inbred C57BL, Tyrosine, MAP kinase, Protein Tyrosine Phosphatase, Mitogen-Activated Protein Kinases, Proto-Oncogene Proteins c-akt, Developmental Biology, Signal Transduction
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