The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase
| Autor: | Catherine Guix, Fabien Llambi, Gabriel del Rio, Laurent Pays, Devrim Gozuacik, Patrick Mehlen, Filipe Calheiros Lourenço, Adi Kimchi |
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| Rok vydání: | 2005 |
| Předmět: |
Transcriptional Activation
Molecular Sequence Data Apoptosis Receptors Cell Surface Biology Mitogen-activated protein kinase kinase Article Catalysis General Biochemistry Genetics and Molecular Biology Mice Animals Immunoprecipitation ASK1 Amino Acid Sequence Nerve Growth Factors Phosphorylation Kinase activity Protein kinase A Molecular Biology Cells Cultured General Immunology and Microbiology MAP kinase kinase kinase Tumor Suppressor Proteins General Neuroscience Autophosphorylation Brain Fibroblasts Netrin-1 Molecular biology Protein Structure Tertiary Cell biology Death-Associated Protein Kinases Death-Associated Protein Kinase 1 Caspases Calcium-Calmodulin-Dependent Protein Kinases Cyclin-dependent kinase 9 Apoptosis Regulatory Proteins Netrin Receptors |
| Zdroj: | The EMBO Journal. 24:1192-1201 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7600584 |
| Popis: | Netrin-1 receptors UNC5H (UNC5H1-4) were originally proposed to mediate the chemorepulsive activity of netrin-1 during axonal guidance processes. However, UNC5H receptors were more recently described as dependence receptors and, as such, able to trigger apoptosis in the absence of netrin-1. They were also proposed as putative tumor suppressors. Here, we show that UNC5H2 physically interacts with the serine/threonine kinase death-associated protein kinase (DAP-kinase) both in cell culture and in embryonic mouse brains. This interaction occurs in part through the respective death domains of UNC5H2 and DAP-kinase. Moreover, part of UNC5H2 proapoptotic activity occurs through this interaction because UNC5H2-induced cell death is partly impaired in the presence of dominant-negative mutants of DAP-kinase or in DAP-kinase mutant murine embryonic fibroblast cells. In the absence of netrin-1, UNC5H2 reduces DAP-kinase autophosphorylation on Ser308 and increases the catalytic activity of the kinase while netrin-1 blocks UNC5H2-dependent DAP-kinase activation. Thus, the pair netrin-1/UNC5H2 may regulate cell fate by controlling the proapoptotic kinase activity of DAP-kinase. |
| Databáze: | OpenAIRE |
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