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Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Physiology

2011

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

Articles 1 - 1 of 1

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Tnf-Stimulated Map Kinase Activation Mediated By A Rho Family Gtpase Signaling Pathway, Shashi Kant, Wojciech Swat, Sheng Zhang, Zhong-Yin Zhang, Benjamin G. Neel, Richard A. Flavell, Roger J. Davis Oct 2011

Tnf-Stimulated Map Kinase Activation Mediated By A Rho Family Gtpase Signaling Pathway, Shashi Kant, Wojciech Swat, Sheng Zhang, Zhong-Yin Zhang, Benjamin G. Neel, Richard A. Flavell, Roger J. Davis

Davis Lab Publications

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.