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Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform.

dc.contributor.author Yan, Dong
dc.contributor.author Jin, Yishi
dc.coverage.spatial United States
dc.date.accessioned 2015-09-16T21:39:01Z
dc.date.issued 2012-11-08
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/23141066
dc.identifier S0896-6273(12)00929-4
dc.identifier.uri https://hdl.handle.net/10161/10618
dc.description.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.
dc.language eng
dc.publisher Elsevier BV
dc.relation.ispartof Neuron
dc.relation.isversionof 10.1016/j.neuron.2012.08.043
dc.subject Animals
dc.subject Caenorhabditis elegans
dc.subject Caenorhabditis elegans Proteins
dc.subject Calcium
dc.subject Enzyme Activation
dc.subject Humans
dc.subject Isoenzymes
dc.subject MAP Kinase Kinase Kinases
dc.subject Mutation
dc.subject Neural Inhibition
dc.title Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform.
dc.type Journal article
duke.contributor.id Yan, Dong|0631346
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/23141066
pubs.begin-page 534
pubs.end-page 548
pubs.issue 3
pubs.organisational-group Basic Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Institute for Brain Sciences
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Neurobiology
pubs.organisational-group School of Medicine
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 76
dc.identifier.eissn 1097-4199


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