UMMS Affiliation

Program in Molecular Medicine

Date

10-1-2011

Document Type

Article

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

Disciplines

Biochemistry | Cell Biology | Cellular and Molecular Physiology | Developmental Biology | Molecular Biology | Molecular Genetics

Abstract

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.

Rights and Permissions

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

Comments

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

Related Resources

Link to Article in PubMed

Keywords

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

PubMed ID

21979919

 
 

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