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Dual leucine zipper kinase

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https://www.readbyqxmd.com/read/27519653/a-role-for-dlk-in-microtubule-reorganization-to-the-cell-periphery-and-in-the-maintenance-of-desmosomal-and-tight-junction-integrity
#1
Carolyne Simard-Bisson, Julie Bidoggia, Danielle Larouche, Sylvain L Guérin, Richard Blouin, Syu-Ichi Hirai, Lucie Germain
Dual leucine zipper-bearing kinase (DLK) is an inducer of keratinocyte differentiation, a complex process also involving microtubule reorganization to the cell periphery. However, signaling mechanisms involved in this process remain to be elucidated. Here, we demonstrate that DLK enhances and is required for microtubule reorganization to the cell periphery in human cell culture models and in Dlk knockout mouse embryos. In tissue-engineered skins with reduced DLK expression, cortical distribution of two microtubule regulators, LIS1 and HSP27, is impaired as well as desmosomal and tight junction integrity...
August 9, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27511108/leucine-zipper-bearing-kinase-promotes-axon-growth-in-mammalian-central-nervous-system-neurons
#2
Meifan Chen, Cédric G Geoffroy, Hetty N Wong, Oliver Tress, Mallorie T Nguyen, Lawrence B Holzman, Yishi Jin, Binhai Zheng
Leucine Zipper-bearing Kinase (LZK/MAP3K13) is a member of the mixed lineage kinase family with high sequence identity to Dual Leucine Zipper Kinase (DLK/MAP3K12). While DLK is established as a key regulator of axonal responses to injury, the role of LZK in mammalian neurons is poorly understood. By gain- and loss-of-function analyses in neuronal cultures, we identify LZK as a novel positive regulator of axon growth. LZK signals specifically through MKK4 and JNKs among MAP2Ks and MAPKs respectively in neuronal cells, with JNK activity positively regulating LZK protein levels...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27468987/dual-leucine-zipper-kinase-regulates-expression-of-axon-guidance-genes-in-mouse-neuronal-cells
#3
Andréanne Blondeau, Jean-François Lucier, Dominick Matteau, Lauralyne Dumont, Sébastien Rodrigue, Pierre-Étienne Jacques, Richard Blouin
BACKGROUND: Recent genetic studies in model organisms, such as Drosophila, C. elegans and mice, have highlighted a critical role for dual leucine zipper kinase (DLK) in neural development and axonal responses to injury. However, exactly how DLK fulfills these functions remains to be determined. Using RNA-seq profiling, we evaluated the global changes in gene expression that are caused by shRNA-mediated knockdown of endogenous DLK in differentiated Neuro-2a neuroblastoma cells. RESULTS: Our analysis led to the identification of numerous up- and down-regulated genes, among which several were found to be associated with system development and axon guidance according to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, respectively...
2016: Neural Development
https://www.readbyqxmd.com/read/27402706/wallenda-dlk-protein-levels-are-temporally-downregulated-by-tramtrack69-to-allow-r7-growth-cones-to-become-stationary-boutons
#4
Alexander I Feoktistov, Tory G Herman
Dual leucine zipper kinase (DLK) promotes growth cone motility and must be restrained to ensure normal development. PHR (Pam/Highwire/RPM-1) ubiquitin ligases therefore target DLK for degradation unless axon injury occurs. Overall DLK levels decrease during development, but how DLK levels are regulated within a developing growth cone has not been examined. We analyzed the expression of the fly DLK Wallenda (Wnd) in R7 photoreceptor growth cones as they halt at their targets and become presynaptic boutons. We found that Wnd protein levels are repressed by the PHR protein Highwire (Hiw) during R7 growth cone halting, as has been observed in other systems...
August 15, 2016: Development
https://www.readbyqxmd.com/read/27350865/regulation-of-microtubule-dynamics-in-axon-regeneration-insights-from-c-elegans
#5
REVIEW
Ngang Heok Tang, Andrew D Chisholm
The capacity of an axon to regenerate is regulated by its external environment and by cell-intrinsic factors. Studies in a variety of organisms suggest that alterations in axonal microtubule (MT) dynamics have potent effects on axon regeneration. We review recent findings on the regulation of MT dynamics during axon regeneration, focusing on the nematode Caenorhabditis elegans. In C. elegans the dual leucine zipper kinase (DLK) promotes axon regeneration, whereas the exchange factor for Arf6 (EFA-6) inhibits axon regeneration...
2016: F1000Research
https://www.readbyqxmd.com/read/27268300/an-evolutionarily-conserved-mechanism-for-camp-elicited-axonal-regeneration-involves-direct-activation-of-the-dual-leucine-zipper-kinase-dlk
#6
Yan Hao, Erin Frey, Choya Yoon, Hetty Wong, Douglas Nestorovski, Lawrence B Holzman, Roman J Giger, Aaron DiAntonio, Catherine Collins
A broadly known method to stimulate the growth potential of axons is to elevate intracellular levels of cAMP, however the cellular pathway(s) that mediate this are not known. Here we identify the Dual Leucine-zipper Kinase (DLK, Wnd in Drosophila) as a critical target and effector of cAMP in injured axons. DLK/Wnd is thought to function as an injury 'sensor', as it becomes activated after axonal damage. Our findings in both Drosophila and mammalian neurons indicate that the cAMP effector kinase PKA is a conserved and direct upstream activator of Wnd/DLK...
June 7, 2016: ELife
https://www.readbyqxmd.com/read/27100796/regulation-of-beta-cell-function-and-mass-by-the-dual-leucine-zipper-kinase
#7
REVIEW
Elke Oetjen
Diabetes mellitus is one of the most rapidly increasing diseases worldwide, whereby approximately 90-95% of patients suffer from type 2 diabetes. Considering its micro- and macrovascular complications like blindness and myocardial infarction, a reliable anti-diabetic treatment is needed. Maintaining the function and the mass of the insulin producing beta-cells despite elevated levels of beta-cell-toxic prediabetic signals represents a desirable mechanism of action of anti-diabetic drugs. The dual leucine zipper kinase (DLK) inhibits the action of two transcription factors within the beta-cell, thereby interfering with insulin secretion and production and the conservation of beta-cell mass...
June 2016: Archiv der Pharmazie
https://www.readbyqxmd.com/read/27084696/tozasertib-attenuates-neuronal-apoptosis-via-dlk-jip3-ma2k7-jnk-pathway-in-early-brain-injury-after-sah-in-rats
#8
Cheng Yin, Guang-Fu Huang, Xiao-Chuan Sun, Zongduo Guo, John H Zhang
BACKGROUND AND PURPOSE: Since tozasertib is neuroprotective for injured optic nerve, this study is intended to test whether tozasertib reduces early brain injury after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Two hundred sixteen (216) male Sprague-Dawley rats were randomly subjected to endovascular perforation model of SAH and sham group. SAH grade, neurological score, and brain water content were measured at 24 and 72 h after SAH. Dual leucine zipper kinase (DLK) and its downstream factors, JNK-interacting protein 3 (JIP3), MA2K7, p-JNK/JNK (c-Jun N-terminal kinase), and apoptosis related proteins cleaved caspase-3 (CC-3), Bim, Bcl-2, and cleaved caspase-9 (CC-9) were analyzed by western blot at 24 h after SAH...
September 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27043251/dual-leucine-zipper-kinase-map3k12-modulators-a-patent-review-2010-2015
#9
Elke Oetjen, Thomas Lemcke
INTRODUCTION: The dual leucine zipper kinase (DLK, MAP3K12) is essential for neuronal development and has been shown to mediate axon regeneration. On the other hand, DLK is involved in the pathogenesis of neurodegenerative disease and diabetes mellitus. Several patents have been published claiming to modulate or inhibit DLK by various approaches including ATP competitive inhibitors. In addition, two publications describe SAR of highly selective DLK inhibitors with efficacy in distinct mouse models of neurodegeneration...
May 2016: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/26933922/oncogenic-roles-of-topk-and-melk-and-effective-growth-suppression-by-small-molecular-inhibitors-in-kidney-cancer-cells
#10
Taigo Kato, Hiroyuki Inoue, Seiya Imoto, Yoshinori Tamada, Takashi Miyamoto, Yo Matsuo, Yusuke Nakamura, Jae-Hyun Park
T-lymphokine-activated killer cell-originated protein kinase (TOPK) and maternal embryonic leucine zipper kinase (MELK) have been reported to play critical roles in cancer cell proliferation and maintenance of stemness. In this study, we investigated possible roles of TOPK and MELK in kidney cancer cells and found their growth promotive effect as well as some feedback mechanism between these two molecules. Interestingly, the blockade of either of these two kinases effectively caused downregulation of forkhead box protein M1 (FOXM1) activity which is known as an oncogenic transcriptional factor in various types of cancer cells...
April 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/26776303/distinct-functions-of-the-dual-leucine-zipper-kinase-depending-on-its-subcellular-localization
#11
Manuel Wallbach, Jorge Duque Escobar, Rohollah Babaeikelishomi, Marie-Jeannette Stahnke, Roland Blume, Sabine Schröder, Jenny Kruegel, Kathrin Maedler, Oliver Kluth, Ralph H Kehlenbach, Nicolai Miosge, Elke Oetjen
The dual leucine zipper kinase DLK induces β-cell apoptosis by inhibiting the transcriptional activity conferred by the β-cell protective transcription factor cAMP response element binding protein CREB. This action might contribute to β-cell loss and ultimately diabetes. Within its kinase domain DLK shares high homology with the mixed lineage kinase (MLK) 3, which is activated by tumor necrosis factor (TNF) α and interleukin (IL)-1β, known prediabetic signals. In the present study, the regulation of DLK in β-cells by these cytokines was investigated...
April 2016: Cellular Signalling
https://www.readbyqxmd.com/read/26719418/palmitoylation-controls-dlk-localization-interactions-and-activity-to-ensure-effective-axonal-injury-signaling
#12
Sabrina M Holland, Kaitlin M Collura, Andrea Ketschek, Kentaro Noma, Toby A Ferguson, Yishi Jin, Gianluca Gallo, Gareth M Thomas
Dual leucine-zipper kinase (DLK) is critical for axon-to-soma retrograde signaling following nerve injury. However, it is unknown how DLK, a predicted soluble kinase, conveys long-distance signals and why homologous kinases cannot compensate for loss of DLK. Here, we report that DLK, but not homologous kinases, is palmitoylated at a conserved site adjacent to its kinase domain. Using short-hairpin RNA knockdown/rescue, we find that palmitoylation is critical for DLK-dependent retrograde signaling in sensory axons...
January 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26657059/dlk-1-p38-map-kinase-signaling-controls-cilium-length-by-regulating-rab-5-mediated-endocytosis-in-caenorhabditis-elegans
#13
Aniek van der Vaart, Suzanne Rademakers, Gert Jansen
Cilia are sensory organelles present on almost all vertebrate cells. Cilium length is constant, but varies between cell types, indicating that cilium length is regulated. How this is achieved is unclear, but protein transport in cilia (intraflagellar transport, IFT) plays an important role. Several studies indicate that cilium length and function can be modulated by environmental cues. As a model, we study a C. elegans mutant that carries a dominant active G protein α subunit (gpa-3QL), resulting in altered IFT and short cilia...
December 2015: PLoS Genetics
https://www.readbyqxmd.com/read/26651941/neuronal-stress-pathway-mediating-a-histone-methyl-phospho-switch-is-required-for-herpes-simplex-virus-reactivation
#14
Anna R Cliffe, Jesse H Arbuckle, Jodi L Vogel, Matthew J Geden, Scott B Rothbart, Corey L Cusack, Brian D Strahl, Thomas M Kristie, Mohanish Deshmukh
Herpes simplex virus (HSV) reactivation from latent neuronal infection requires stimulation of lytic gene expression from promoters associated with repressive heterochromatin. Various neuronal stresses trigger reactivation, but how these stimuli activate silenced promoters remains unknown. We show that a neuronal pathway involving activation of c-Jun N-terminal kinase (JNK), common to many stress responses, is essential for initial HSV gene expression during reactivation. This JNK activation in neurons is mediated by dual leucine zipper kinase (DLK) and JNK-interacting protein 3 (JIP3), which direct JNK toward stress responses instead of other cellular functions...
December 9, 2015: Cell Host & Microbe
https://www.readbyqxmd.com/read/26124562/identification-of-collaborative-activities-with-oxidative-phosphorylation-in-bipolar-disorder
#15
Hashime Sawai, Takako Takai-Igarashi, Hiroshi Tanaka
UNLABELLED: Bipolar disorder (BD) is a psychiatric disease considered to polygenic with multiple factors in genetics, each of which is not dominant but collaborative during pathogenic progression. We describe a method that estimates the collaborative contribution to the disease between a certain well-studied pathway and the other candidate pathway using Gene Set Enrichment Analysis (GSEA). We describe a modified GSEA (improved derivation) to identify genes that are significantly and differentially expressed between disease and non-disease states and that are consistently co-expressed with a target pathway which is deeply related to disease etiology...
2015: Bioinformation
https://www.readbyqxmd.com/read/25802931/akt-suppresses-dlk-for-maintaining-self-renewal-of-mouse-embryonic-stem-cells
#16
Cheng-Chung Wu, Hong-Jin Wu, Chia-Hui Wang, Chia-Hua Lin, Shu-Ching Hsu, Yi-Rong Chen, Michael Hsiao, Scott C Schuyler, Frank Leigh Lu, Nianhan Ma, Jean Lu
Mouse embryonic stem cells (ES cells) can proliferate indefinitely. To identify potential signals involved in suppression of self-renewal, we previously screened a kinase/phosphatase expression library in ES cells, and observed that inhibition of Dual Leucine zipper-bearing Kinase (DLK) increased relative cell numbers. DLK protein was detected in both the pluripotent and differentiated states of mouse ES cells while DLK kinase activity increased upon differentiation. Overexpression of DLK in mouse ES cells displayed reductions in relative cell/colony numbers and Nanog expression, suggesting a suppressive role of DLK in self-renewal...
2015: Cell Cycle
https://www.readbyqxmd.com/read/25726747/cytoskeletal-disruption-activates-the-dlk-jnk-pathway-which-promotes-axonal-regeneration-and-mimics-a-preconditioning-injury
#17
Vera Valakh, Erin Frey, Elisabetta Babetto, Lauren J Walker, Aaron DiAntonio
Nerve injury can lead to axonal regeneration, axonal degeneration, and/or neuronal cell death. Remarkably, the MAP3K dual leucine zipper kinase, DLK, promotes each of these responses, suggesting that DLK is a sensor of axon injury. In Drosophila, mutations in proteins that stabilize the actin and microtubule cytoskeletons activate the DLK pathway, suggesting that DLK may be activated by cytoskeletal disruption. Here we test this model in mammalian sensory neurons. We find that pharmacological agents designed to disrupt either the actin or microtubule cytoskeleton activate the DLK pathway, and that activation is independent of calcium influx or induction of the axon degeneration program...
May 2015: Neurobiology of Disease
https://www.readbyqxmd.com/read/25589918/dual-leucine-zipper-kinase-inhibitors-potential-treatments-for-neurodegenerative-diseases
#18
Ahmed F Abdel-Magid
No abstract text is available yet for this article.
January 8, 2015: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/25359212/rhgf-1-pdz-rhogef-and-retrograde-dlk-1-signaling-drive-neuronal-remodeling-on-microtubule-disassembly
#19
Chun-Hao Chen, Albert Lee, Chien-Po Liao, Ya-Wen Liu, Chun-Liang Pan
Neurons remodel their connectivity in response to various insults, including microtubule disruption. How neurons sense microtubule disassembly and mount remodeling responses by altering genetic programs in the soma are not well defined. Here we show that in response to microtubule disassembly, the Caenorhabditis elegans PLM neuron remodels by retracting its synaptic branch and overextending the primary neurite. This remodeling required RHGF-1, a PDZ-Rho guanine nucleotide exchange factor (PDZ-RhoGEF) that was associated with and inhibited by microtubules...
November 18, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/25143472/bisphenol-a-enhances-adipogenic-differentiation-of-human-adipose-stromal-stem-cells
#20
Jason F Ohlstein, Amy L Strong, John A McLachlan, Jeffrey M Gimble, Matthew E Burow, Bruce A Bunnell
Exposure of humans to the endocrine disrupter bisphenol A (BPA) has been associated with increased weight and obesity. However, the mechanism(s) by which BPA increases adipose tissue in humans remains to be determined. The goal of this study was to determine the effects of BPA on adipogenesis of cultured human adipose stromal/stem cells (ASCs), precursors to mature adipocytes. ASCs from three donors were cultured for either 14 or 21 days in adipogenic differentiation media containing increasing concentrations of BPA (100 pM-10 μM)...
December 2014: Journal of Molecular Endocrinology
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