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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)2069-2078
Number of pages10
JournalGenes and Development
Volume25
Issue number19
DOIs
StatePublished - Oct 1 2011

Keywords

  • MAP kinase
  • MLK
  • Mixed-lineage protein kinase
  • TNF

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    Kant, S., Swat, W., Zhang, S., Zhang, Z. Y., Neel, B. G., Flavell, R. A., & Davis, R. J. (2011). TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway. Genes and Development, 25(19), 2069-2078. https://doi.org/10.1101/gad.17224711