Dclk1

Summary

Gene Symbol: Dclk1
Description: doublecortin-like kinase 1
Alias: 1700113D08Rik, 2810480F11Rik, AI836758, Click-I, Cpg16, Dcamkl1, Dcl, Dclk, mKIAA0369, serine/threonine-protein kinase DCLK1, CLICK-I beta, doublecortin and calcium/calmodulin-dependent protein kinase-like 1, doublecortin-like and CAM kinase-like 1
Species: mouse
Products:     Dclk1

Top Publications

  1. Burgess H, Martinez S, Reiner O. KIAA0369, doublecortin-like kinase, is expressed during brain development. J Neurosci Res. 1999;58:567-75 pubmed
    ..doublecortin-like region, and the third containing only the kinase domain, a homolog of the previously cloned rat CPG16 gene...
  2. Omori Y, Suzuki M, Ozaki K, Harada Y, Nakamura Y, Takahashi E, et al. Expression and chromosomal localization of KIAA0369, a putative kinase structurally related to Doublecortin. J Hum Genet. 1998;43:169-77 pubmed
    ..Human KIAA0369 was mapped by fluorescence in situ hybridization (FISH) to chromosome 13q13-q14.1. The presence of genes related to neuropathy has been reported in this locus. ..
  3. Deuel T, Liu J, Corbo J, Yoo S, Rorke Adams L, Walsh C. Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron. 2006;49:41-53 pubmed
    ..A second locus, doublecortin-like kinase (Dclk), encodes a protein with similar "doublecortin domains" and microtubule stabilization properties that may ..
  4. Sossey Alaoui K, Srivastava A. DCAMKL1, a brain-specific transmembrane protein on 13q12.3 that is similar to doublecortin (DCX). Genomics. 1999;56:121-6 pubmed
    ..We have designated this protein DCAMKL1. It maps to chromosome 13q12.3-q13, within a 540-kb YAC clone containing markers D13S805 and D13S1164...
  5. Liu J, Schubert C, Fu X, Fourniol F, Jaiswal J, Houdusse A, et al. Molecular basis for specific regulation of neuronal kinesin-3 motors by doublecortin family proteins. Mol Cell. 2012;47:707-21 pubmed publisher
    ..Neurons lacking Dcx and/or its structurally conserved paralogue, doublecortin-like kinase 1 (Dclk1), show impaired Kif1a-mediated transport of Vamp2, a cargo of Kif1a, with decreased run length...
  6. Engels B, Schouten T, van Dullemen J, Gosens I, Vreugdenhil E. Functional differences between two DCLK splice variants. Brain Res Mol Brain Res. 2004;120:103-14 pubmed
    Recently, we have cloned two splice variants of the doublecortin-like kinase (DCLK) gene, called DCLK-short-A and -B, both of which encode calcium/calmodulin-dependent protein kinase (CaMK)-like proteins with different C-terminal ends...
  7. Saaltink D, Håvik B, Verissimo C, Lucassen P, Vreugdenhil E. Doublecortin and doublecortin-like are expressed in overlapping and non-overlapping neuronal cell population: implications for neurogenesis. J Comp Neurol. 2012;520:2805-23 pubmed publisher
    We have characterized the expression of doublecortin-like (DCL), a microtubule-associated protein involved in embryonic neurogenesis that is highly homologous to doublecortin (DCX), in the adult mouse brain...
  8. Tuy F, Saillour Y, Kappeler C, Chelly J, Francis F. Alternative transcripts of Dclk1 and Dclk2 and their expression in doublecortin knockout mice. Dev Neurosci. 2008;30:171-86 pubmed
    ..DCX) gene, mutated in X-linked human lissencephaly, has 2 close paralogs, doublecortin-like kinase 1 and 2 (Dclk1 and 2)...
  9. Lin P, Gleeson J, Corbo J, Flanagan L, Walsh C. DCAMKL1 encodes a protein kinase with homology to doublecortin that regulates microtubule polymerization. J Neurosci. 2000;20:9152-61 pubmed
    Doublecortin (DCX) is a microtubule-associated protein required for neuronal migration to the cerebral cortex. DCAMKL1 consists of an N terminus that is 65% similar to DCX throughout the entire length of DCX, but also contains an ..

More Information

Publications56

  1. May R, Riehl T, Hunt C, Sureban S, Anant S, Houchen C. Identification of a novel putative gastrointestinal stem cell and adenoma stem cell marker, doublecortin and CaM kinase-like-1, following radiation injury and in adenomatous polyposis coli/multiple intestinal neoplasia mice. Stem Cells. 2008;26:630-7 pubmed
    ..Thus, nuclear translocation of beta-catenin distinguishes normal and adenoma stem cells. Targeting DCAMKL-1 may represent a strategy for developing novel chemotherapeutic agents. ..
  2. Ohmae S, Takemoto Kimura S, Okamura M, Adachi Morishima A, Nonaka M, Fuse T, et al. Molecular identification and characterization of a family of kinases with homology to Ca2+/calmodulin-dependent protein kinases I/IV. J Biol Chem. 2006;281:20427-39 pubmed
    ..CL1alpha and CL1beta were shorter isoforms of DCAMKL1, which lacked the doublecortin-like domain (Dx)...
  3. Burgess H, Reiner O. Alternative splice variants of doublecortin-like kinase are differentially expressed and have different kinase activities. J Biol Chem. 2002;277:17696-705 pubmed
    ..variants of DCLK and examine the expression profile of two splice variants affecting the kinase domain of DCLK and CPG16 (candidate plasticity gene 16), one containing an Arg-rich domain and the other affecting the C terminus of the ..
  4. Bailey J, Alsina J, Rasheed Z, McAllister F, Fu Y, Plentz R, et al. DCLK1 marks a morphologically distinct subpopulation of cells with stem cell properties in preinvasive pancreatic cancer. Gastroenterology. 2014;146:245-56 pubmed publisher
    ..The microtubule regulator DCLK1 marked a morphologically distinct and functionally unique population of pancreatic cancer-initiating cells...
  5. Fitzsimons C, Ahmed S, Wittevrongel C, Schouten T, Dijkmans T, Scheenen W, et al. The microtubule-associated protein doublecortin-like regulates the transport of the glucocorticoid receptor in neuronal progenitor cells. Mol Endocrinol. 2008;22:248-62 pubmed
    ..of function studies, we report here for the first time that the microtubule-associated protein doublecortin-like (DCL) controls GR translocation to the nucleus...
  6. Koizumi H, Tanaka T, Gleeson J. Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration. Neuron. 2006;49:55-66 pubmed
    ..Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline ..
  7. Vreugdenhil E, Kolk S, Boekhoorn K, Fitzsimons C, Schaaf M, Schouten T, et al. Doublecortin-like, a microtubule-associated protein expressed in radial glia, is crucial for neuronal precursor division and radial process stability. Eur J Neurosci. 2007;25:635-48 pubmed
    ..Although the microtubule-associated proteins doublecortin (DCX) and doublecortin-like kinase (DCLK) are critically involved in dynamic rearrangement of the cytoskeletal machinery that allow migration, little is ..
  8. Nakanishi Y, Seno H, Fukuoka A, Ueo T, Yamaga Y, Maruno T, et al. Dclk1 distinguishes between tumor and normal stem cells in the intestine. Nat Genet. 2013;45:98-103 pubmed publisher
    ..To identify a potential TSC-specific marker, we focused on doublecortin-like kinase 1 (Dclk1)...
  9. Bjerknes M, Khandanpour C, Moroy T, Fujiyama T, Hoshino M, Klisch T, et al. Origin of the brush cell lineage in the mouse intestinal epithelium. Dev Biol. 2012;362:194-218 pubmed publisher
  10. Shu T, Tseng H, Sapir T, Stern P, Zhou Y, Sanada K, et al. Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression. Neuron. 2006;49:25-39 pubmed
    ..a group of developmentally enriched microtubule-associated proteins (MAPs) including doublecortin-like kinase (DCLK), a protein that shares high homology with doublecortin (DCX)...
  11. Baek S, Kerjan G, Bielas S, Lee J, Fenstermaker A, Novarino G, et al. Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous microRNA dysregulation. Neuron. 2014;82:1255-1262 pubmed publisher
    ..This effect was not limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-..
  12. Sureban S, May R, Qu D, Weygant N, Chandrakesan P, Ali N, et al. DCLK1 regulates pluripotency and angiogenic factors via microRNA-dependent mechanisms in pancreatic cancer. PLoS ONE. 2013;8:e73940 pubmed publisher
    ..We have previously demonstrated that downregulation of DCLK1 can upregulate critical miRNAs in both in vitro and in vivo cancer models and results in downregulation of c-MYC, ..
  13. Tanaka T, Koizumi H, Gleeson J. The doublecortin and doublecortin-like kinase 1 genes cooperate in murine hippocampal development. Cereb Cortex. 2006;16 Suppl 1:i69-73 pubmed
    The doublecortin (Dcx) and doublecortin-like kinase 1 (Dclk) genes are developmentally expressed neuronal microtubule-associated proteins...
  14. May R, Qu D, Weygant N, Chandrakesan P, Ali N, Lightfoot S, et al. Brief report: Dclk1 deletion in tuft cells results in impaired epithelial repair after radiation injury. Stem Cells. 2014;32:822-7 pubmed publisher
    The role of Dclk1(+) tuft cells in the replacement of intestinal epithelia and reestablishing the epithelial barrier after severe genotoxic insult is completely unknown...
  15. Tsang W, Shek K, Lee T, Chow K. An evolutionarily conserved nested gene pair - Mab21 and Lrba/Nbea in metazoan. Genomics. 2009;94:177-87 pubmed publisher
  16. Westphalen C, Takemoto Y, Tanaka T, Macchini M, Jiang Z, Renz B, et al. Dclk1 Defines Quiescent Pancreatic Progenitors that Promote Injury-Induced Regeneration and Tumorigenesis. Cell Stem Cell. 2016;18:441-55 pubmed publisher
    ..Using genetic lineage tracing, we show that Doublecortin-like kinase-1 (Dclk1) labels a rare population of long-lived, quiescent pancreatic cells...
  17. Kruidering M, Schouten T, Evan G, Vreugdenhil E. Caspase-mediated cleavage of the Ca2+/calmodulin-dependent protein kinase-like kinase facilitates neuronal apoptosis. J Biol Chem. 2001;276:38417-25 pubmed
    ..Together, our data suggest that cleavage of CaMKLK and generation of the noncatalytic N-terminal domain of CaMKLK facilitate neuronal apoptosis. ..
  18. Nawabi H, Belin S, Cartoni R, Williams P, Wang C, Latremolière A, et al. Doublecortin-Like Kinases Promote Neuronal Survival and Induce Growth Cone Reformation via Distinct Mechanisms. Neuron. 2015;88:704-19 pubmed publisher
    ..Multifunctional DCXs thus represent potential targets for promoting both survival and regeneration of injured neurons. ..
  19. Westphalen C, Asfaha S, Hayakawa Y, Takemoto Y, Lukin D, Nuber A, et al. Long-lived intestinal tuft cells serve as colon cancer-initiating cells. J Clin Invest. 2014;124:1283-95 pubmed
    Doublecortin-like kinase 1 protein (DCLK1) is a gastrointestinal tuft cell marker that has been proposed to identify quiescent and tumor growth-sustaining stem cells...
  20. Shin E, Kashiwagi Y, Kuriu T, Iwasaki H, Tanaka T, Koizumi H, et al. Doublecortin-like kinase enhances dendritic remodelling and negatively regulates synapse maturation. Nat Commun. 2013;4:1440 pubmed publisher
    ..Thus, doublecortin-like kinases are critical regulators of dendritic development by means of their specific targeting to the distal dendrites, and their local control of dendritic growth and synapse maturation. ..
  21. Hayakawa Y, Sakitani K, Konishi M, Asfaha S, Niikura R, Tomita H, et al. Nerve Growth Factor Promotes Gastric Tumorigenesis through Aberrant Cholinergic Signaling. Cancer Cell. 2017;31:21-34 pubmed publisher
    ..Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1+ tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa...
  22. Goto N, Ueo T, Fukuda A, Kawada K, Sakai Y, Miyoshi H, et al. Distinct Roles of HES1 in Normal Stem Cells and Tumor Stem-like Cells of the Intestine. Cancer Res. 2017;77:3442-3454 pubmed publisher
    ..Notably, in Lgr5+ or Dclk1+ tumor stem cells derived from established intestinal tumors, Hes1 deletion triggered immediate ..
  23. Saqui Salces M, Keeley T, Grosse A, Qiao X, El Zaatari M, Gumucio D, et al. Gastric tuft cells express DCLK1 and are expanded in hyperplasia. Histochem Cell Biol. 2011;136:191-204 pubmed publisher
    ..Additional tuft cell markers, e.g., doublecortin-like kinase 1 (DCLK1), were used to co-localize with acTub...
  24. Zou W, Greenblatt M, Brady N, Lotinun S, Zhai B, de Rivera H, et al. The microtubule-associated protein DCAMKL1 regulates osteoblast function via repression of Runx2. J Exp Med. 2013;210:1793-806 pubmed publisher
    ..This functional genomics analysis led to the identification of the microtubule-associated protein DCAMKL1 (Doublecortin-like and CAM kinase-like 1) as a novel regulator of osteogenesis...
  25. Schenk G, Veldhuisen B, Wedemeier O, McGown C, Schouten T, Oitzl M, et al. Over-expression of ?C-DCLK-short in mouse brain results in a more anxious behavioral phenotype. Physiol Behav. 2010;101:541-8 pubmed publisher
    Products of the Doublecortin-Like Kinase (DCLK) gene are associated with cortical migration and hippocampal maturation during embryogenesis...
  26. Schenk G, Werkman T, Wadman W, Veldhuisen B, Dijkmans T, Blaas E, et al. Over-expression of the DCLK gene transcript CARP decreases CA3/CA1 network excitability. Brain Res. 2010;1352:21-34 pubmed publisher
    Products of the Doublecortin Like Kinase (DCLK) gene are implicated in cortical migration and hippocampal maturation during embryogenesis...
  27. Qu D, Weygant N, May R, Chandrakesan P, Madhoun M, Ali N, et al. Ablation of Doublecortin-Like Kinase 1 in the Colonic Epithelium Exacerbates Dextran Sulfate Sodium-Induced Colitis. PLoS ONE. 2015;10:e0134212 pubmed publisher
    Doublecortin-like kinase 1 (Dclk1), a microtubule-associated kinase, marks the fifth lineage of intestinal epithelial cells called tuft cells that function as tumor stem cells in Apc mutant models of colon cancer...
  28. Westphalen C, Quante M, Wang T. Functional implication of Dclk1 and Dclk1-expressing cells in cancer. Small Gtpases. 2017;8:164-171 pubmed publisher
    ..Originally designated Doublecortin and CaM kinase-like 1 protein (Dcamkl1) or KIAA0369, Dclk1 was first described as a marker for radial glia cells in the context of microtubule ..
  29. Sobecki M, Mrouj K, Camasses A, Parisis N, Nicolas E, Llères D, et al. The cell proliferation antigen Ki-67 organises heterochromatin. elife. 2016;5:e13722 pubmed publisher
    ..Altogether, our results suggest that Ki-67 expression in proliferating cells spatially organises heterochromatin, thereby controlling gene expression. ..
  30. Kechele D, Blue R, Zwarycz B, Espenschied S, Mah A, Siegel M, et al. Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation. J Clin Invest. 2017;127:593-607 pubmed publisher
    ..Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling-induced proliferation, particularly during regeneration and adenoma formation. ..
  31. Du A, McCracken K, Walp E, Terry N, Klein T, Han A, et al. Arx is required for normal enteroendocrine cell development in mice and humans. Dev Biol. 2012;365:175-88 pubmed publisher
    ..Taken together, our findings uncover a novel and conserved role of Arx in mammalian endocrine cell development and provide a potential cause for the chronic diarrhea seen in both humans and mice carrying Arx mutations. ..
  32. Basak O, Beumer J, Wiebrands K, Seno H, van Oudenaarden A, Clevers H. Induced Quiescence of Lgr5+ Stem Cells in Intestinal Organoids Enables Differentiation of Hormone-Producing Enteroendocrine Cells. Cell Stem Cell. 2017;20:177-190.e4 pubmed publisher
    ..Our observations uncouple Wnt-dependent stem cell maintenance from EGF-dependent proliferation and provide an approach for the study of the elusive EECs in a defined environment. ..
  33. Vreugdenhil E, Engels B, Middelburg R, van Koningsbruggen S, Knol J, Veldhuisen B, et al. Multiple transcripts generated by the DCAMKL gene are expressed in the rat hippocampus. Brain Res Mol Brain Res. 2001;94:67-74 pubmed
    ..We conclude that alternative splicing of the DCAMKL gene may generate different but similar proteins in the adult rat hippocampus thereby regulating different but overlapping aspects of DCAMKL controlled neuronal plasticity. ..
  34. Qu D, May R, Sureban S, Weygant N, Chandrakesan P, Ali N, et al. Inhibition of Notch signaling reduces the number of surviving Dclk1+ reserve crypt epithelial stem cells following radiation injury. Am J Physiol Gastrointest Liver Physiol. 2014;306:G404-11 pubmed publisher
    We have previously reported that doublecortin-like kinase 1 (Dclk1) is a putative intestinal stem cell (ISC) marker...
  35. Dijkmans T, van Hooijdonk L, Fitzsimons C, Vreugdenhil E. The doublecortin gene family and disorders of neuronal structure. Cent Nerv Syst Agents Med Chem. 2010;10:32-46 pubmed
    ..In addition, to generate new hypotheses for further research, we analyzed the serine, threonine and proline-rich domain for predicted protein interactions. ..
  36. Fu X, Brown K, Yap C, Winckler B, Jaiswal J, Liu J. Doublecortin (Dcx) family proteins regulate filamentous actin structure in developing neurons. J Neurosci. 2013;33:709-21 pubmed publisher
    ..We show with that the phenotype of Dcx/Doublecortin-like kinase 1 deficiency is consistent with actin defect, as these axons are selectively deficient in axon guidance, but not elongation. ..
  37. Mao H, McMahon J, Tsai Y, Wang Z, Silver D. Haploinsufficiency for Core Exon Junction Complex Components Disrupts Embryonic Neurogenesis and Causes p53-Mediated Microcephaly. PLoS Genet. 2016;12:e1006282 pubmed publisher
    ..Altogether our study reveals new mechanisms to help explain how EJC mutations influence neurogenesis and underlie neurodevelopmental disease. ..
  38. Walker T, Yasuda T, Adams D, Bartlett P. The doublecortin-expressing population in the developing and adult brain contains multipotential precursors in addition to neuronal-lineage cells. J Neurosci. 2007;27:3734-42 pubmed
    ..These results indicate that DCX(high) cells, regardless of location, are restricted to the neuronal lineage or are bone fide neurons, whereas some DCX(low) cells retain their multipotentiality. ..
  39. Friocourt G, Koulakoff A, Chafey P, Boucher D, Fauchereau F, Chelly J, et al. Doublecortin functions at the extremities of growing neuronal processes. Cereb Cortex. 2003;13:620-6 pubmed
    ..The observations summarized here favor the suggestion that whereas LIS1 may play a role in nuclear migration, Doublecortin is instead restricted to functions at the leading edge of the cell. ..
  40. Chandrakesan P, May R, Weygant N, Qu D, Berry W, Sureban S, et al. Intestinal tuft cells regulate the ATM mediated DNA Damage response via Dclk1 dependent mechanism for crypt restitution following radiation injury. Sci Rep. 2016;6:37667 pubmed publisher
    ..The function of Dclk1 expressing tuft cells regulating intestinal epithelial DNA damage response for cell survival/self-renewal after ..
  41. Chandrakesan P, Yao J, Qu D, May R, Weygant N, Ge Y, et al. Dclk1, a tumor stem cell marker, regulates pro-survival signaling and self-renewal of intestinal tumor cells. Mol Cancer. 2017;16:30 pubmed publisher
    ..Doublecortin-like kinase 1 (Dclk1), a kinase protein, is overexpressed in colorectal cancer and specifically marks tumor stem cells (TSCs) that self-..
  42. Shintani T, Takeuchi Y, Fujikawa A, Noda M. Directional neuronal migration is impaired in mice lacking adenomatous polyposis coli 2. J Neurosci. 2012;32:6468-84 pubmed publisher
    ..Thus, APC2 is an essential mediator of the cytoskeletal regulation at leading edges in response to extracellular signals. ..
  43. Burgess H, Reiner O. Cleavage of doublecortin-like kinase by calpain releases an active kinase fragment from a microtubule anchorage domain. J Biol Chem. 2001;276:36397-403 pubmed
    ..The isolated kinase domain retains catalytic activity and is structurally similar to CPG16, a second product of the DCLK gene expressed in the adult brain that lacks the doublecortin domain...
  44. Choi E, Petersen C, Lapierre L, Williams J, Weis V, Goldenring J, et al. Dynamic expansion of gastric mucosal doublecortin-like kinase 1-expressing cells in response to parietal cell loss is regulated by gastrin. Am J Pathol. 2015;185:2219-31 pubmed publisher
    Doublecortin-like kinase 1 (Dclk1) is considered a reliable marker for tuft cells in the gastrointestinal tract...
  45. Chandrakesan P, Weygant N, May R, Qu D, Chinthalapally H, Sureban S, et al. DCLK1 facilitates intestinal tumor growth via enhancing pluripotency and epithelial mesenchymal transition. Oncotarget. 2014;5:9269-80 pubmed
    Doublecortin-like kinase 1 (Dclk1) is overexpressed in many cancers including colorectal cancer (CRC) andit specifically marks intestinal tumor stem cells...
  46. Friocourt G, Liu J, Antypa M, Rakic S, Walsh C, Parnavelas J. Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration. J Neurosci. 2007;27:3875-83 pubmed
    ..A similar delay in interneuron migration was observed when Doublecortin-like kinase (DCLK), a microtubule-associated protein related to DCX, was inactivated, although the morphology of the cells was not ..
  47. Boekhoorn K, Sarabdjitsingh A, Kommerie H, de Punder K, Schouten T, Lucassen P, et al. Doublecortin (DCX) and doublecortin-like (DCL) are differentially expressed in the early but not late stages of murine neocortical development. J Comp Neurol. 2008;507:1639-52 pubmed publisher
    ..The microtubule-associated proteins doublecortin (DCX) and doublecortin-like (DCL) are critically involved in neuronal migration and division, and may function in a partially redundant pathway...