UMMS Affiliation

Program in Molecular Medicine

Publication Date


Document Type



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.


MAP kinase, MLK, mixed-lineage protein kinase, TNF

Rights and Permissions

Freely available online through the Genes and Development Open Access option.

DOI of Published Version



Genes Dev. 2011 Oct 1;25(19):2069-78. doi: 10.1101/gad.17224711. Link to article on publisher's site

Journal/Book/Conference Title

Genes and development

Related Resources

Link to Article in PubMed

PubMed ID




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