![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 16, Issue 8, 3562-3573, August 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Institut National de la Santé et de la Recherche Médicale U584, Faculté de Médecine Necker-Enfants Malades, 75730 Paris Cedex 15, France
Submitted December 16, 2004;
Revised April 25, 2005;
Accepted May 13, 2005
Monitoring Editor: Gerard Evan
Dual-specificity tyrosine-phosphorylated and regulated kinase 1A (Dyrk1A) is the human homologue of the Drosophila mnb (minibrain) gene. In Drosophila, mnb is involved in postembryonic neurogenesis. In human, DYRK1A maps within the Down syndrome critical region of chromosome 21 and is overexpressed in Down syndrome embryonic brain. Despite its potential involvement in the neurobiological alterations observed in Down syndrome patients, the biological functions of the serine/threonine kinase DYRK1A have not been identified yet. Here, we report that DYRK1A overexpression potentiates nerve growth factor (NGF)-mediated PC12 neuronal differentiation by up-regulating the Ras/MAP kinase signaling pathway independently of its kinase activity. Furthermore, we show that DYRK1A prolongs the kinetics of ERK activation by interacting with Ras, B-Raf, and MEK1 to facilitate the formation of a Ras/B-Raf/MEK1 multiprotein complex. These data indicate that DYRK1A may play a critical role in Ras-dependent transducing signals that are required for promoting or maintaining neuronal differentiation and suggest that overexpression of DYRK1A may contribute to the neurological abnormalities observed in Down syndrome patients.
Abbreviations used: DYRK1A, dual-specificity tyrosine-phosphorylated and regulated kinase 1A; FKHR, Forkhead in rhabdomyosarcoma; GDP, guanosine 5'-diphosphate; GST, glutathione S-transferase; GTP
S, 5'-O-(3-thio)triphosphate; MAPK, mitogen-activated protein kinase; mnb, minibrain; NGF, nerve growth factor; siRNA, small interfering RNA.
* Present address: CNRS UMR 8542, Ecole Normale Supérieure, 46 Rue d'Ulm, 75230 Paris Cedex 05, France.
Address correspondence to: Zohra Rahmani (rahmani{at}biologie.ens.fr).
This article has been cited by other articles:
|
|
 |
|
  T. M. E. Scales, S. Lin, M. Kraus, R. G. Goold, and P. R. Gordon-Weeks Nonprimed and DYRK1A-primed GSK3{beta}-phosphorylation sites on MAP1B regulate microtubule dynamics in growing axons J. Cell Sci., July 15, 2009; 122(14): 2424 - 2435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fernandez-Martinez, E. M. Vela, M. Tora-Ponsioen, O. H. Ocana, M. A. Nieto, and J. Galceran Attenuation of Notch signalling by the Down-syndrome-associated kinase DYRK1A J. Cell Sci., May 15, 2009; 122(10): 1574 - 1583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-Y. Yang and M.-C. Hung A New Fork for Clinical Application: Targeting Forkhead Transcription Factors in Cancer Clin. Cancer Res., February 1, 2009; 15(3): 752 - 757. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Aranda, M. Alvarez, S. Turro, A. Laguna, and S. de la Luna Sprouty2-Mediated Inhibition of Fibroblast Growth Factor Signaling Is Modulated by the Protein Kinase DYRK1A Mol. Cell. Biol., October 1, 2008; 28(19): 5899 - 5911. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Alvarez, X. Altafaj, S. Aranda, and S. de la Luna DYRK1A Autophosphorylation on Serine Residue 520 Modulates Its Kinase Activity via 14-3-3 Binding Mol. Biol. Cell, April 1, 2007; 18(4): 1167 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Pellegrini-Calace and A. Tramontano Identification of a novel putative mitogen-activated kinase cascade on human chromosome 21 by computational approaches Bioinformatics, April 1, 2006; 22(7): 775 - 778. [Abstract] [Full Text] [PDF]
|
|
