Reference - Detail
| RRC ID | 46476 |
|---|---|
| Author | Yan D, Jin Y. |
| Title | Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform. |
| Journal | Neuron |
| Abstract |
MAPKKK dual leucine zipper-bearing kinases (DLKs) are regulators of synaptic development and axon regeneration. The mechanisms underlying their activation are not fully understood. Here, we show that C. elegans DLK-1 is activated by a Ca(2+)-dependent switch from inactive heteromeric to active homomeric protein complexes. We identify a DLK-1 isoform, DLK-1S, that shares identical kinase and leucine zipper domains with the previously described long isoform DLK-1L but acts to inhibit DLK-1 function by binding to DLK-1L. The switch between homo- or heteromeric DLK-1 complexes is influenced by Ca(2+) concentration. A conserved hexapeptide in the DLK-1L C terminus is essential for DLK-1 activity and is required for Ca(2+) regulation. The mammalian DLK-1 homolog MAP3K13 contains an identical C-terminal hexapeptide and can functionally complement dlk-1 mutants, suggesting that the DLK activation mechanism is conserved. The DLK activation mechanism is ideally suited for rapid and spatially controlled signal transduction in response to axonal injury and synaptic activity. |
| Volume | 76(3) |
| Pages | 534-48 |
| Published | 2012-11-8 |
| DOI | 10.1016/j.neuron.2012.08.043 |
| PII | S0896-6273(12)00929-4 |
| PMID | 23141066 |
| PMC | PMC3508676 |
| MeSH | Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / antagonists & inhibitors* Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Calcium / physiology* Enzyme Activation / physiology Humans Isoenzymes / antagonists & inhibitors Isoenzymes / metabolism Isoenzymes / physiology MAP Kinase Kinase Kinases / antagonists & inhibitors* MAP Kinase Kinase Kinases / metabolism MAP Kinase Kinase Kinases / physiology* Mutation / physiology Neural Inhibition / physiology* |
| IF | 14.415 |
| Times Cited | 62 |
| WOS Category | NEUROSCIENCES |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | F1000Research |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm4024 |