Article: article from journal or magazin.
MEK kinase 1 gene disruption alters cell migration and c-Jun NH2-terminal kinase regulation but does not cause a measurable defect in NF-kappa B activation.
Proceedings of the National Academy of Sciences of the United States of America
Publication types: Publication Status: ppublish
MEK kinase 1 (MEKK1) is a 196-kDa mitogen-activated protein kinase (MAPK) kinase kinase that, in addition to regulating the c-Jun NH(2)-terminal kinase (JNK) pathway, is involved in the control of cell motility. MEKK1(-/-) mice are defective in eyelid closure, a TGFalpha-directed process involving the migration of epithelial cells. MEKK1 expression in epithelial cells stimulates lamellipodia formation, a process required for cell movement. In addition, mouse embryo fibroblasts derived from MEKK1(-/-) mice are inhibited in their migration relative to MEKK1(+/+) fibroblasts. MEKK1 is required for JNK but not NF-kappaB activation in response to virus infection, microtubule disruption, and stimulation of embryonic stem cells with lysophosphatidic acid. MEKK1 is not required for TNFalpha or IL-1 regulation of JNK or NF-kappaB activation in macrophages or fibroblasts. Thus, MEKK1 senses microtubule integrity, contributes to the regulation of fibroblast and epithelial cell migration, and is required for activation of JNK but not NF-kappaB in response to selected stress stimuli.
UI="D000818">Animals, UI="D002465">Cell Movement/UI="Q000235">genetics, UI="D002478">Cells, Cultured, UI="D005347">Fibroblasts/UI="Q000166">cytology, UI="D005347">Fibroblasts/UI="Q000502">physiology, UI="D017353">Gene Deletion, UI="D005786">Gene Expression Regulation, UI="D048031">JNK Mitogen-Activated Protein Kinases, UI="D048728">MAP Kinase Kinase Kinase 1, UI="D051379">Mice, UI="D018345">Mice, Knockout, UI="D020928">Mitogen-Activated Protein Kinases/UI="Q000235">genetics, UI="D016328">NF-kappa B/UI="Q000235">genetics, UI="D017346">Protein-Serine-Threonine Kinases/UI="Q000235">genetics, UI="D015398">Signal Transduction/UI="Q000235">genetics
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