TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway
Open Access
- 1 October 2011
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 25 (19) , 2069-2078
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.Keywords
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