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 language | English |
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Pages (from-to) | 2069-2078 |
Number of pages | 10 |
Journal | Genes and Development |
Volume | 25 |
Issue number | 19 |
DOIs | |
State | Published - Oct 1 2011 |
Keywords
- MAP kinase
- MLK
- Mixed-lineage protein kinase
- TNF