Role of MLK3 in the regulation of mitogen-activated protein kinase signaling cascades

D Brancho, JJ Ventura, A Jaeschke… - … and cellular biology, 2005 - Taylor & Francis
D Brancho, JJ Ventura, A Jaeschke, B Doran, RA Flavell, RJ Davis
Molecular and cellular biology, 2005Taylor & Francis
Mixed-lineage protein kinase 3 (MLK3) is a member of the mitogen-activated protein (MAP)
kinase kinase kinase group that has been implicated in multiple signaling cascades,
including the NF-κB pathway and the extracellular signal-regulated kinase, c-Jun NH2-
terminal kinase (JNK), and p38 MAP kinase pathways. Here, we examined the effect of
targeted disruption of the murine Mlk3 gene. Mlk3−/− mice were found to be viable and
healthy. Primary embryonic fibroblasts prepared from these mice exhibited no major …
Mixed-lineage protein kinase 3 (MLK3) is a member of the mitogen-activated protein (MAP) kinase kinase kinase group that has been implicated in multiple signaling cascades, including the NF-κB pathway and the extracellular signal-regulated kinase, c-Jun NH2-terminal kinase (JNK), and p38 MAP kinase pathways. Here, we examined the effect of targeted disruption of the murine Mlk3 gene. Mlk3−/− mice were found to be viable and healthy. Primary embryonic fibroblasts prepared from these mice exhibited no major signaling defects. However, we did find that MLK3 deficiency caused a selective reduction in tumor necrosis factor (TNF)-stimulated JNK activation. Together, these data demonstrate that MLK3 contributes to the TNF signaling pathway that activates JNK.
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