Title
Role of MLK3 in the regulation of mitogen-activated protein kinase signaling cascades
GSBS Program
Biochemistry & Molecular Pharmacology
UMMS Affiliation
Graduate School of Biomedical Sciences; Program in Molecular Medicine
Date
4-16-2005
Document Type
Article
Medical Subject Headings
Adipocytes; Animals; Cell Differentiation; Cell Proliferation; Enzyme Activation; Epidermis; Gene Silencing; Gene Targeting; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase Kinases; *MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinase Kinases; NF-kappa B; Phosphorylation; Transcription Factor AP-1; Tumor Necrosis Factor-alpha; p38 Mitogen-Activated Protein Kinases
Disciplines
Life Sciences | Medicine and Health Sciences
Abstract
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-kappaB pathway and the extracellular signal-regulated kinase, c-Jun NH(2)-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.
Rights and Permissions
Citation: Mol Cell Biol. 2005 May;25(9):3670-81. Link to article on publisher's site