Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

DLK (Dual Leucine Zipper-Bearing Kinase)

  • Richard Blouin
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_402

Synonyms

Historical Background

DLK is a serine/threonine kinase that belongs to the mixed-lineage kinase (MLK) family of mitogen-activated protein kinase kinase kinases (MAPKKKs) (Gallo and Johnson 2002). It was discovered in 1994 as a protein differentially expressed during the retinoic acid-induced neuronal differentiation of human NT2 teratocarcinoma cells and originally denoted zipper protein kinase (ZPK) (Reddy and Pleasure 1994). Parallel and subsequent studies led to the identification and cloning of the mouse and rat homologs of ZPK, respectively, termed DLK (Holzman et al. 1994) and MAP kinase upstream kinase (MUK) (Hirai et al. 1996).

Structure, Expression, and Subcellular Localization

DLK is a protein of about 120 kDa that shares with other...
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Notes

Acknowledgments

We thank Dr. Alain Lavigueur for critical reading of the manuscript and the Natural Sciences and Engineering Research Council of Canada for its financial support. We also apologize to our colleagues whose work could not be cited due to space limitations.

References

  1. Baker ST, Opperman KJ, Tulgren ED, Turgeon SM, 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.  https://doi.org/10.1371/journal.pgen.1004297.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bloom AJ, Miller BR, Sanes JR, DiAntonio A. The requirement for Phr1 in CNS axon tract formation reveals the corticostriatal boundary as a choice point for cortical axons. Genes Dev. 2007;21:2593–606.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Chen CH, Lee A, Liao CP, Liu YW, Pan CL. RHGF-1/PDZ-RhoGEF and retrograde DLK-1 signaling drive neuronal remodeling on microtubule disassembly. Proc Natl Acad Sci USA. 2014;111:16568–73.  https://doi.org/10.1073/pnas.1410263111.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Collins CA, Wairkar YP, Johnson SL, DiAntonio A. Highwire restrains synaptic growth by attenuating a MAP kinase signal. Neuron. 2006;51:57–69.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Couture JP, Daviau A, Fradette J, Blouin R. The mixed-lineage kinase DLK is a key regulator of 3T3-L1 adipocyte differentiation. PLoS One. 2009;4:e4743.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Daviau A, Di Fruscio M, Blouin R. The mixed-lineage kinase DLK undergoes Src-dependent tyrosine phosphorylation and activation in cells exposed to vanadate or platelet-derived growth factor (PDGF). Cell Signal. 2009;21:577–87.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Eto K, Kawauchi T, Osawa M, Tabata H, Nakajima K. Role of dual leucine zipper-bearing kinase (DLK/MUK/ZPK) in axonal growth. Neurosci Res. 2010;66:37–45.CrossRefPubMedGoogle Scholar
  8. Fan G, Merritt SE, Kortenjann M, Shaw PE, Holzman LB. Dual leucine zipper-bearing kinase (DLK) activates p46(SAPK) and p38(mapk) but not ERK2. J Biol Chem. 1996;271:24788–93.CrossRefPubMedGoogle Scholar
  9. Fukuyama K, Yoshida M, Yamashita A, Deyama T, Baba M, Suzuki A, et al. MAPK upstream kinase (MUK)-binding inhibitory protein, a negative regulator of MUK/dual leucine zipper-bearing kinase/leucine zipper protein kinase. J Biol Chem. 2000;275:21247–54.CrossRefPubMedGoogle Scholar
  10. Gallo KA, Johnson GL. Mixed-lineage kinase control of JNK and p38 MAPK pathways. Nat Rev Mol Cell Biol. 2002;3:663–72.CrossRefPubMedGoogle Scholar
  11. Ghosh AS, Wang B, Pozniak CD, Chen M, Watts RJ, Lewcock JW. DLK induces developmental neuronal degeneration via selective regulation of proapoptotic JNK activity. J Cell Biol. 2011;194:751–64.  https://doi.org/10.1083/jcb.201103153.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Hammarlund M, Nix P, Hauth L, Jorgensen EM, Bastiani M. Axon regeneration requires a conserved MAP kinase pathway. Science. 2009;323:802–6.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Hao Y, Frey E, Yoon C, Wong H, Nestorovski D, Holzman LB, Giger RJ, DiAntonio A, Collins C. An evolutionarily conserved mechanism for cAMP elicited axonal regeneration involves direct activation of the dual leucine zipper kinase DLK. Elife. 2016;5:e14048.  https://doi.org/10.7554/eLife.14048.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hirai S, Izawa M, Osada S, Spyrou G, Ohno S. Activation of the JNK pathway by distantly related protein kinases. MEKK and MUK Oncogene. 1996;12:641–50.PubMedGoogle Scholar
  15. Hirai S, Kawaguchi A, Hirasawa R, Baba M, Ohnishi T, Ohno S. MAPK-upstream protein kinase (MUK) regulates the radial migration of immature neurons in telencephalon of mouse embryo. Development. 2002;129:4483–95.PubMedGoogle Scholar
  16. Hirai S, de Cui F, Miyata T, Ogawa M, Kiyonari H, Suda Y, et al. The c-Jun N-terminal kinase activator dual leucine zipper kinase regulates axon growth and neuronal migration in the developing cerebral cortex. J Neurosci. 2006;26:11992–2002.CrossRefPubMedGoogle Scholar
  17. Hirai S, Banba Y, Satake T, Ohno S. Axon formation in neocortical neurons depends on stage-specific regulation of microtubule stability by the dual leucine zipper kinase-c-Jun N-terminal kinase pathway. J Neurosci. 2011;31:6468–80.  https://doi.org/10.1523/JNEUROSCI.5038-10.2011.CrossRefPubMedGoogle Scholar
  18. Holland SM, Collura KM, Ketschek A, Noma K, Ferguson TA, Jin Y, Gallo G, Thomas GM. Palmitoylation controls DLK localization, interactions and activity to ensure effective axonal injury signaling. Proc Natl Acad Sci USA. 2016;113:763–8.  https://doi.org/10.1073/pnas.1514123113.CrossRefPubMedGoogle Scholar
  19. Holzman LB, Merritt SE, Fan G. Identification, molecular cloning, and characterization of dual leucine zipper bearing kinase. A novel serine/threonine protein kinase that defines a second subfamily of mixed lineage kinases. J Biol Chem. 1994;269:30808–17.PubMedGoogle Scholar
  20. Huntwork-Rodriguez S, Wang B, Watkins T, Ghosh AS, Pozniak CD, Bustos D, Newton K, Kirkpatrick DS, Lewcock JW. JNK-mediated phosphorylation of DLK suppresses its ubiquitination to promote neuronal apoptosis. J Cell Biol. 2013;202:747–63.  https://doi.org/10.1083/jcb.201303066.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Itoh A, Horiuchi M, Wakayama K, Xu J, Bannerman P, Pleasure D, Itoh T. ZPK/DLK, a mitogen-activated protein kinase kinase kinase, is a critical mediator of programmed cell death of motoneurons. J Neurosci. 2011;31:7223–8.  https://doi.org/10.1523/JNEUROSCI.5947-10.2011.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Miller BR, Press C, Daniels RW, Sasaki Y, Milbrandt J, DiAntonio A. A dual leucine kinase-dependent axon self-destruction program promotes Wallerian degeneration. Nat Neurosci. 2009;12:387–9.PubMedPubMedCentralCrossRefGoogle Scholar
  23. Nadeau A, Grondin G, Blouin R. In situ hybridization analysis of ZPK gene expression during murine embryogenesis. J Histochem Cytochem. 1997;45:107–18.CrossRefPubMedGoogle Scholar
  24. Nakata K, Abrams B, Grill B, Goncharov A, Huang X, Chisholm AD, 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.CrossRefPubMedGoogle Scholar
  25. Pozniak CD, Sengupta Ghosh A, Gogineni A, Hanson JE, Lee SH, Larson JL, et al. Dual leucine zipper kinase is required for excitotoxicity-induced neuronal degeneration. J Exp Med. 2013;210:2553–67.  https://doi.org/10.1084/jem.20122832.CrossRefPubMedPubMedCentralGoogle Scholar
  26. Reddy UR, Pleasure D. Cloning of a novel putative protein kinase having a leucine zipper domain from human brain. Biochem Biophys Res Commun. 1994;202:613–20.CrossRefPubMedGoogle Scholar
  27. Robitaille H, Proulx R, Robitaille K, Blouin R, Germain L. The mitogen-activated protein kinase kinase kinase dual leucine zipper-bearing kinase (DLK) acts as a key regulator of keratinocyte terminal differentiation. J Biol Chem. 2005;280:12732–41.CrossRefPubMedGoogle Scholar
  28. Robitaille K, Daviau A, Lachance G, Couture JP, Blouin R. Calphostin C-induced apoptosis is mediated by a tissue transglutaminase-dependent mechanism involving the DLK/JNK signaling pathway. Cell Death Differ. 2008;15:1522–31.CrossRefPubMedGoogle Scholar
  29. Shin JE, Cho Y, Beirowski B, Milbrandt J, Cavalli V, DiAntonio A. Dual leucine zipper kinase is required for retrograde injury signaling and axonal regeneration. Neuron. 2012;74:1015–22.  https://doi.org/10.1016/j.neuron.2012.04.028.CrossRefPubMedPubMedCentralGoogle Scholar
  30. Stahnke MJ, Dickel C, Schröder S, Kaiser D, Blume R, Stein R, et al. Inhibition of human insulin gene transcription and MafA transcriptional activity by the dual leucine zipper kinase. Cell Signal. 2014;26:1792–9.  https://doi.org/10.1016/j.cellsig.2014.04.006.CrossRefPubMedPubMedCentralGoogle Scholar
  31. Valakh V, Walker LJ, Skeath JB, DiAntonio A. Loss of the spectraplakin short stop activates the DLK injury response pathway in Drosophila. J Neurosci. 2013;33:17863–73.  https://doi.org/10.1523/JNEUROSCI.2196-13.2013.CrossRefPubMedPubMedCentralGoogle Scholar
  32. Valakh V, Frey E, Babetto E, Walker LJ, DiAntonio A. Cytoskeletal disruption activates the DLK/JNK pathway, which promotes axonal regeneration and mimics a preconditioning injury. Neurobiol Dis. 2015;77:13–25.  https://doi.org/10.1016/j.nbd.2015.02.014.CrossRefPubMedPubMedCentralGoogle Scholar
  33. Wallbach M, Duque Escobar J, Babaeikelishomi R, Stahnke MJ, Blume R, Schröder S, et al. Distinct functions of the dual leucine zipper kinase depending on its subcellular localization. Cell Signal. 2016;28:272–83.  https://doi.org/10.1016/j.cellsig.2016.01.002.CrossRefPubMedGoogle Scholar
  34. Watkins TA, Wang B, Huntwork-Rodriguez S, Yang J, Jiang Z, Eastham-Anderson J, et al. DLK initiates a transcriptional program that couples apoptotic and regenerative responses to axonal injury. Proc Natl Acad Sci USA. 2013;110:4039–44.  https://doi.org/10.1073/pnas.1211074110.CrossRefPubMedPubMedCentralGoogle Scholar
  35. Welsbie DS, Yang Z, Ge Y, Mitchell KL, Zhou X, Martin SE, et al. Functional genomic screening identifies dual leucine zipper kinase as a key mediator of retinal ganglion cell death. Proc Natl Acad Sci USA. 2013;110:4045–50.  https://doi.org/10.1073/pnas.1211284110.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Wu CC, Wu HJ, Wang CH, Lin CH, Hsu SC, Chen YR, et al. Akt suppresses DLK for maintaining self-renewal of mouse embryonic stem cells. Cell Cycle. 2015;14:1207–17.  https://doi.org/10.1080/15384101.2015.1014144.CrossRefPubMedPubMedCentralGoogle Scholar
  37. Xu Z, Maroney AC, Dobrzanski P, Kukekov NV, Greene LA. The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis. Mol Cell Biol. 2001;21:4713–24.PubMedPubMedCentralCrossRefGoogle Scholar
  38. Yan D, Jin Y. Regulation of DLK-1 kinase activity by calcium-mediated dissociation from an inhibitory isoform. Neuron. 2012;76:534–48.  https://doi.org/10.1016/j.neuron.2012.08.043.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Département de biologieUniversité de SherbrookeSherbrookeCanada