title: TNF-stimulated MAP kinase activation mediated by a Rho family GTPase signaling pathway.
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.
authors: Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors: Shashi
authors: S
authors: Kant
authors: Wojciech
authors: W
authors: Swat
authors: Sheng
authors: S
authors: Zhang
authors: Zhong-Yin
authors: ZY
authors: Zhang
authors: Benjamin G
authors: BG
authors: Neel
authors: Richard A
authors: RA
authors: Flavell
authors: Roger J
authors: RJ
authors: Davis
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation; D007249:Inflammation / Q000201:enzymology; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D051567:Proto-Oncogene Proteins c-vav; D014409:Tumor Necrosis Factor-alpha; D014443:Tyrosine; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; C516609:Ptpn1 protein, mouse; D020764:cdc42 GTP-Binding Protein