Program in Molecular Medicine
Medical Subject Headings
Animals; Cells, Cultured; Enzyme Activation; Inflammation; Mice; Mice, Inbred C57BL; Mitogen-Activated Protein Kinases; Phosphorylation; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-vav; *Signal Transduction; Tumor Necrosis Factor-alpha; Tyrosine; cdc42 GTP-Binding Protein
Biochemistry | Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology | Molecular Genetics
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.
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Citation: Genes Dev. 2011 Oct 1;25(19):2069-78. doi: 10.1101/gad.17224711. Link to article on publisher's site
MAP kinase, MLK, mixed-lineage protein kinase, TNF
Kant, Shashi; Swat, Wojciech; Zhang, Sheng; Zhang, Zhong-Yin; Neel, Benjamin G.; Flavell, Richard A.; and Davis, Roger J., "TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway" (2011). Davis Lab Publications. 39.