Skip to main content
SpringerLink
Log in

Dyrk1a

  • Living reference work entry
  • First Online:
Encyclopedia of Signaling Molecules

  • 321 Accesses

Synonyms

Dual specificity tyrosine-phosphorylation regulated kinase 1A; Dual specificity Yak1-related kinase 1A; Dyrk1A; DYRK1A; hMNB; Minibrain; mnb; Mnb; MNB; MNBH; Protein kinase minibrain homolog

Historical Background

DYRK1A is a member of the Mnb/DYRK subfamily of protein kinases, which falls within the CMGC Ser/Thr family to which cyclin-dependent kinases (CDKs), CDC-like kinases (CLKs), glycogen synthase kinase (GSK3), and mitogen-activated protein kinase (MAPK) also belong. The founding member of the Mnb/DYRK subfamily in multicellular organisms was identified in Drosophila melanogaster (Dm) and due to the reduced brain size associated with its loss of function it was named minibrain (mnb). This phenotype is caused by altered proliferation during brain development, suggesting a key function for this kinase in the regulation of neural proliferation and neurogenesis (Tejedor et al. 1995). In addition, mnbmutant flies have behavioral defects, indicative of alterations to...

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Altafaj X, Dierssen M, Baamonde C, Marti E, Visa J, Guimera J, et al. Neurodevelopmental delay, motor abnormalities and cognitive deficits in transgenic mice overexpressing Dyrk1A (minibrain), a murine model of Down’s syndrome. Hum Mol Genet. 2001;10(18):1915–23.

    Article  CAS  PubMed  Google Scholar 

  • Aranda S, Laguna A, de la Luna S. DYRK family of protein kinases: Evolutionary relationships, biochemical properties, and functional roles. FASEB J. 2011;25(2):449–62.

    Article  CAS  PubMed  Google Scholar 

  • Arron JR, Winslow MM, Polleri A, Chang CP, Wu H, Gao X, et al. NFAT dysregulation by increased dosage of DSCR1 and DYRK1A on chromosome 21. Nature. 2006;441(7093):595–600.

    Article  CAS  PubMed  Google Scholar 

  • Becker W, Sippl W. Activation, regulation, and inhibition of DYRK1A. FEBS J. 2011;278(2):246–56.

    Article  CAS  PubMed  Google Scholar 

  • Becker W, Soppa U, Tejedor FJ. DYRK1A: a potential drug target for multiple Down syndrome neuropathologies. CNS Neurol Disord Drug Targets. 2014;13(1):26–33.

    Article  CAS  PubMed  Google Scholar 

  • Chen CK, Bregere C, Paluch J, Lu JF, Dickman DK, Chang KT. Activity-dependent facilitation of Synaptojanin and synaptic vesicle recycling by the Minibrain kinase. Nat Commun. 2014;5:4246.

    CAS  PubMed  PubMed Central  Google Scholar 

  • da Costa Martins PA, Salic K, Gladka MM, Armand AS, Leptidis S, el Azzouzi H, et al. MicroRNA-199b targets the nuclear kinase Dyrk1a in an auto-amplification loop promoting calcineurin/NFAT signalling. Nat Cell Biol. 2010;12(12):1220–7.

    Article  PubMed  Google Scholar 

  • Degoutin JL, Milton CC, Yu E, Tipping M, Bosveld F, Yang L, et al. Riquiqui and minibrain are regulators of the hippo pathway downstream of Dachsous. Nat Cell Biol. 2013;15(10):1176–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferron SR, Pozo N, Laguna A, Aranda S, Porlan E, Moreno M, et al. Regulated segregation of kinase Dyrk1A during asymmetric neural stem cell division is critical for EGFR-mediated biased signaling. Cell Stem Cell. 2010;7(3):367–79.

    Article  CAS  PubMed  Google Scholar 

  • Fotaki V, Dierssen M, Alcantara S, Martinez S, Marti E, Casas C, et al. Dyrk1A haploinsufficiency affects viability and causes developmental delay and abnormal brain morphology in mice. Mol Cell Biol. 2002;22(18):6636–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guimera J, Casas C, Pucharcos C, Solans A, Domenech A, Planas AM, et al. A human homologue of Drosophila minibrain (MNB) is expressed in the neuronal regions affected in Down syndrome and maps to the critical region. Hum Mol Genet. 1996;5(9):1305–10.

    Article  CAS  PubMed  Google Scholar 

  • Hammerle B, Ulin E, Guimera J, Becker W, Guillemot F, Tejedor FJ. Transient expression of Mnb/Dyrk1a couples cell cycle exit and differentiation of neuronal precursors by inducing p27KIP1 expression and suppressing NOTCH signaling. Development. 2011;138(12):2543–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Himpel S, Tegge W, Frank R, Leder S, Joost HG, Becker W. Specificity determinants of substrate recognition by the protein kinase DYRK1A. J Biol Chem. 2000;275(4):2431–8.

    Article  CAS  PubMed  Google Scholar 

  • Hong SH, Lee KS, Kwak SJ, Kim AK, Bai H, Jung MS, et al. Minibrain/Dyrk1a regulates food intake through the Sir2-FOXO-sNPF/NPY pathway in Drosophila and mammals. PLoS Genet. 2012;8(8):e1002857.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kentrup H, Becker W, Heukelbach J, Wilmes A, Schurmann A, Huppertz C, et al. Dyrk, a dual specificity protein kinase with unique structural features whose activity is dependent on tyrosine residues between subdomains VII and VIII. J Biol Chem. 1996;271(7):3488–95.

    Article  CAS  PubMed  Google Scholar 

  • Lochhead PA, Sibbet G, Morrice N, Cleghon V. Activation-loop autophosphorylation is mediated by a novel transitional intermediate form of DYRKs. Cell. 2005;121:925–36.

    Article  CAS  PubMed  Google Scholar 

  • Schneider P, Bayo-Fina JM, Singh R, Kumar Dhanyamraju P, Holz P, Baier A, et al. Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1. Nat Commun. 2015;6:8023.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shaikh MN, Gutierrez-Avino F, Colonques J, Ceron J, Hammerle B, Tejedor FJ. Minibrain drives the Dacapo-dependent cell cycle exit of neurons in the Drosophila brain by promoting asense and prospero expression. Development. 2016;143(17):3195–205.

    Article  CAS  PubMed  Google Scholar 

  • Soppa U, Schumacher J, Florencio Ortiz V, Pasqualon T, Tejedor FJ, Becker W. The Down syndrome-related protein kinase DYRK1A phosphorylates p27(Kip1) and Cyclin D1 and induces cell cycle exit and neuronal differentiation. Cell Cycle. 2014;13(13):2084–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tejedor F, Zhu XR, Kaltenbach E, Ackermann A, Baumann A, Canal I, et al. Minibrain: a new protein kinase family involved in postembryonic neurogenesis in Drosophila. Neuron. 1995;14(2):287–301.

    Article  CAS  PubMed  Google Scholar 

  • Tejedor FJ, Hammerle B. MNB/DYRK1A as a multiple regulator of neuronal development. FEBS J. 2011;278(2):223–35.

    Article  CAS  PubMed  Google Scholar 

  • Tschop K, Conery AR, Litovchick L, Decaprio JA, Settleman J, Harlow E, et al. A kinase shRNA screen links LATS2 and the pRB tumor suppressor. Genes Dev. 2011;25(8):814–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang P, Alvarez-Perez JC, Felsenfeld DP, Liu H, Sivendran S, Bender A, et al. A high-throughput chemical screen reveals that harmine-mediated inhibition of DYRK1A increases human pancreatic beta cell replication. Nat Med. 2015;21(4):383–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wegiel J, Gong CX, Hwang YW. The role of DYRK1A in neurodegenerative diseases. FEBS J. 2011;278(2):236–45.

    Article  CAS  PubMed  Google Scholar 

  • Xie W, Adayev T, Zhu H, Wegiel J, Wieraszko A, Hwang YW. Activity-dependent phosphorylation of dynamin 1 at serine 857. Biochemistry. 2012;51(34):6786–96.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Instituto de Neurociencias, CSIC and Universidad Miguel Hernandez-Campus de San Juan, 03550, Sant Joan (Alicante), Spain

    Francisco J. Tejedor

Authors
  1. Francisco J. Tejedor
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Francisco J. Tejedor .

Editor information

Editors and Affiliations

  1. Dept. Biological Science, Department of Molecular Science and Tech College of Natural Science, Suwon, Korea (Republic of)

    Sangdun Choi

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media LLC

About this entry

Cite this entry

Tejedor, F.J. (2016). Dyrk1a. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6438-9_101613-1

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6438-9_101613-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, New York, NY

  • Online ISBN: 978-1-4614-6438-9

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Search

Navigation