MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6
| Autor: | L A, Tibbles, Y L, Ing, F, Kiefer, J, Chan, N, Iscove, J R, Woodgett, N J, Lassam |
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| Rok vydání: | 1996 |
| Předmět: |
Mitogen-Activated Protein Kinase Kinases
MAP Kinase Kinase 4 MAP Kinase Kinase 3 JNK Mitogen-Activated Protein Kinases Protein Serine-Threonine Kinases Protein-Tyrosine Kinases MAP Kinase Kinase Kinases Cell Line Enzyme Activation COS Cells Calcium-Calmodulin-Dependent Protein Kinases Animals Humans Mitogen-Activated Protein Kinases Phosphorylation Protein Kinases HeLa Cells Protein Binding Signal Transduction Research Article |
| Zdroj: | The EMBO journal. 15(24) |
| ISSN: | 0261-4189 |
| Popis: | Mixed lineage kinase-3 (MLK-3) is a 97 kDa serine/threonine kinase with multiple interaction domains, including a Cdc42 binding motif, but unknown function. Cdc42 and the related small GTP binding protein Rac1 can activate the SAPK/JNK and p38/RK stress-responsive kinase cascades, suggesting that MLK-3 may have a role in upstream regulation of these pathways. In support of this role, we demonstrate that MLK-3 can specifically activate the SAPK/JNK and p38/RK pathways, but has no effect on the activation of ERKs. Immunoprecipitated MLK-3 catalyzed the phosphorylation of SEK1 in vitro, and co-transfected MLK-3 induced phosphorylation of SEK1 and MKK3 at sites required for activation, suggesting direct regulation of these protein kinases. Furthermore, interactions between MLK-3 and SEK and MLK-3 and MKK6 were observed in co-precipitation experiments. Finally, kinase-dead mutants of MLK-3 blocked activation of the SAPK pathway by a newly identified mammalian analog of Ste20, germinal center kinase, but not by MEKK, suggesting that MLK-3 functions to activate the SAPK/JNK and p38/RK cascades in response to stimuli transduced by Ste20-like kinases. |
| Databáze: | OpenAIRE |
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