Gene Symbol: dlk-1
Description: Dual-Leucine zipper Kinase;Mitogen-activated protein kinase kinase kinase dlk-1
Alias: Dual-Leucine zipper Kinase;Mitogen-activated protein kinase kinase kinase dlk-1
Species: Caenorhabditis elegans

Top Publications

  1. Nakata K, Abrams B, Grill B, Goncharov A, Huang X, Chisholm A, et al. Regulation of a DLK-1 and p38 MAP kinase pathway by the ubiquitin ligase RPM-1 is required for presynaptic development. Cell. 2005;120:407-20 pubmed
    ..DLK-1 protein levels are elevated in rpm-1 mutants. The RPM-1 RING finger can stimulate ubiquitination of DLK-1. Our data reveal a presynaptic role of a previously unknown p38 MAP kinase cascade. ..
  2. Hammarlund M, Nix P, Hauth L, Jorgensen E, Bastiani M. Axon regeneration requires a conserved MAP kinase pathway. Science. 2009;323:802-6 pubmed publisher
    ..We conclude that after axon injury, activation of this MAP kinase cascade is required to switch the mature neuron from an aplastic state to a state capable of growth. ..
  3. Park E, Glodowski D, Rongo C. The ubiquitin ligase RPM-1 and the p38 MAPK PMK-3 regulate AMPA receptor trafficking. PLoS ONE. 2009;4:e4284 pubmed publisher
    ..Our findings indicate a novel specialized role for RPM-1 and PMK-3/p38 MAPK in regulating the endosomal trafficking of AMPARs at central synapses. ..
  4. Yan D, Wu Z, Chisholm A, Jin Y. The DLK-1 kinase promotes mRNA stability and local translation in C. elegans synapses and axon regeneration. Cell. 2009;138:1005-18 pubmed publisher
    ..Our findings identify the DLK-1 pathway as a regulator of mRNA stability in synapse formation and maintenance and also in adult axon regeneration. ..
  5. Nix P, Hisamoto N, Matsumoto K, Bastiani M. Axon regeneration requires coordinate activation of p38 and JNK MAPK pathways. Proc Natl Acad Sci U S A. 2011;108:10738-43 pubmed publisher
    ..These two MAPKs are coregulated by the E3 ubiquitin ligase RPM-1(Phr1) via targeted degradation of the MAPKKKs DLK-1 and MLK-1 and by the MAPK phosphatase VHP-1(MKP7), which negatively regulates both PMK-3(p38) and KGB-1(JNK). ..
  6. Ghosh Roy A, Wu Z, Goncharov A, Jin Y, Chisholm A. Calcium and cyclic AMP promote axonal regeneration in Caenorhabditis elegans and require DLK-1 kinase. J Neurosci. 2010;30:3175-83 pubmed publisher
    ..These findings reveal the relationship between Ca(2+)/cAMP signaling and the DLK-1 MAPK (mitogen-activated protein kinase) cascade in regeneration. ..
  7. Yan D, Jin Y. Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform. Neuron. 2012;76:534-48 pubmed publisher
    ..The DLK activation mechanism is ideally suited for rapid and spatially controlled signal transduction in response to axonal injury and synaptic activity. ..
  8. O Brien G, Sagasti A. Fragile axons forge the path to gene discovery: a MAP kinase pathway regulates axon regeneration. Sci Signal. 2009;2:pe30 pubmed publisher
    ..Understanding how the DLK-1 pathway acts in development, plasticity, and regeneration may shed light on the evolution of mechanisms regulating axon regeneration. ..
  9. Chen C, Lee A, Liao C, Liu Y, Pan C. RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly. Proc Natl Acad Sci U S A. 2014;111:16568-73 pubmed publisher
    ..Our data represent a neuronal remodeling paradigm during development that reshapes the neural circuit by the coordinated removal of the dysfunctional synaptic branch compartment and compensatory extension of the primary neurite. ..

More Information


  1. Holland S, Collura K, Ketschek A, Noma K, Ferguson T, Jin Y, et al. Palmitoylation controls DLK localization, interactions and activity to ensure effective axonal injury signaling. Proc Natl Acad Sci U S A. 2016;113:763-8 pubmed publisher
    ..These findings explain how DLK specifically mediates nerve injury responses and reveal a novel cellular mechanism that ensures the specificity of neuronal kinase signaling. ..
  2. Munk√°csy E, Khan M, Lane R, Borror M, Park J, Bokov A, et al. DLK-1, SEK-3 and PMK-3 Are Required for the Life Extension Induced by Mitochondrial Bioenergetic Disruption in C. elegans. PLoS Genet. 2016;12:e1006133 pubmed publisher
    ..In those mitochondrial bioenergetic mutants which activate Ptbb-6::GFP, we find that dlk-1, sek-3 and pmk-3 are all required for their life extension. ..
  3. Han S, Baig H, Hammarlund M. Mitochondria Localize to Injured Axons to Support Regeneration. Neuron. 2016;92:1308-1323 pubmed publisher
    ..These data identify regulation of axonal mitochondria as a new cell-biological mechanism that helps determine the regenerative response of injured neurons. ..
  4. Li C, Hisamoto N, Nix P, Kanao S, Mizuno T, Bastiani M, et al. The growth factor SVH-1 regulates axon regeneration in C. elegans via the JNK MAPK cascade. Nat Neurosci. 2012;15:551-7 pubmed publisher
    ..Thus, SVH-1-SVH-2 signaling via activation of the MAPK pathway acts to coordinate neuron regeneration response after axon injury. ..
  5. Baker S, Opperman K, Tulgren E, Turgeon S, Bienvenut W, Grill B. RPM-1 uses both ubiquitin ligase and phosphatase-based mechanisms to regulate DLK-1 during neuronal development. PLoS Genet. 2014;10:e1004297 pubmed publisher
    ..Thus, PHR proteins are potentially more accurate and sensitive regulators of DLK than originally thought. Our results also highlight an important and expanding role for the PP2C phosphatase family in neuronal development. ..