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Genes Dev. 2011 Oct 1;25(19):2069-78. doi: 10.1101/gad.17224711.

TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway.

Author information

  • 1Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.

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.

PMID:
21979919
[PubMed - indexed for MEDLINE]
PMCID:
PMC3197205
Free PMC Article

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