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

2011; Cold Spring Harbor Laboratory Press; Volume: 25; Issue: 19 Linguagem: Inglês

10.1101/gad.17224711

1549-5477

Shashi Kant, Wojciech Swat, Sheng Zhang, Zhong-Yin Zhang, Benjamin G. Neel, Richard A. Flavell, Roger J. Davis,

NF-κB Signaling Pathways

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.