SEK1 deficiency reveals mitogen-activated protein kinase cascade crossregulation and leads to abnormal hepatogenesis
| Autor: | Leonard I. Zon, Yuko Fujiwara, Tohru Ikeda, Lia Kwee, Andrew C. Perkins, Soula Ganiatsas, Mark A. Labow |
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| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
MAP Kinase Kinase 4
p38 mitogen-activated protein kinases Mitogen-activated protein kinase kinase Biology Mice medicine Animals Protein kinase A Fibroblast Mice Knockout Mitogen-Activated Protein Kinase Kinases Multidisciplinary Kinase Stem Cells Gene Expression Regulation Developmental Biological Sciences Fibroblasts Molecular biology Cell biology medicine.anatomical_structure Liver Calcium-Calmodulin-Dependent Protein Kinases Phosphorylation Signal transduction Stem cell Protein Kinases Signal Transduction |
| Popis: | SEK1 (MKK4/JNKK) is a mitogen-activated protein kinase activator that has been shown to participate in vitro in two stress-activated cascades terminating with the SAPK and p38 kinases. To define the role of SEK1 in vivo , we studied stress-induced signaling in SEK1 −/− embryonic stem and fibroblast cells and evaluated the phenotype of SEK1 −/− mouse embryos during development. Studies of SEK1 −/− embryonic stem cells demonstrated defects in stimulated SAPK phosphorylation but not in the phosphorylation of p38 kinase. In contrast, SEK1 −/− fibroblasts exhibited defects in both SAPK and p38 phosphorylation, demonstrating that crosstalk exists between the stress-activated cascades. Tumor necrosis factor α and interleukin 1 stimulation of both stress-activated cascades are severely affected in the SEK1 −/− fibroblast cells. SEK1 deficiency leads to embryonic lethality after embryonic day 12.5 and is associated with abnormal liver development. This phenotype is similar to c-jun null mouse embryos and suggests that SEK1 is required for phosphorylation and activation of c-jun during the organo-genesis of the liver. |
| Databáze: | OpenAIRE |
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