Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform.
Cobertura |
United States |
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Data(s) |
08/11/2012
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Resumo |
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. |
Formato |
534 - 548 |
Identificador |
http://www.ncbi.nlm.nih.gov/pubmed/23141066 S0896-6273(12)00929-4 Neuron, 2012, 76 (3), pp. 534 - 548 http://hdl.handle.net/10161/10618 1097-4199 |
Idioma(s) |
ENG |
Relação |
Neuron 10.1016/j.neuron.2012.08.043 |
Palavras-Chave | #Animals #Caenorhabditis elegans #Caenorhabditis elegans Proteins #Calcium #Enzyme Activation #Humans #Isoenzymes #MAP Kinase Kinase Kinases #Mutation #Neural Inhibition |
Tipo |
Journal Article |