 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
Previous Article | Next Article
The Journal of Neuroscience, June 15, 2002, 22(12):4869-4877
Cyclin-Dependent Kinase 5 Phosphorylates Disabled 1 Independently of Reelin Signaling
Lakhu Keshvara, Susan Magdaleno, David Benhayon, and Tom Curran Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105
Two major signaling pathways that control neuronal positioning during brain development have been uncovered as a result of genetic and biochemical studies on neurological mouse mutants. Mice deficient in Reelin, Disabled 1 (Dab1), or both the very low-density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor 2 (ApoER2) exhibit identical neuroanatomic defects in laminar structures throughout the brain. These proteins function as components of the Reelin signaling pathway. Reelin is a secreted glycoprotein that binds to VLDLR and ApoER2, inducing tyrosine phosphorylation of Dab1, an intracellular adapter protein. Neuronal migration is also regulated by cyclin-dependent kinase 5 (Cdk5) and its activating subunits p35 and p39. Mice deficient in Cdk5, p35, or both p35 and p39 exhibit lamination defects that are similar but not identical to those observed in mice with a defect in the Reelin signaling pathway. Cdk5 phosphorylates proteins that maintain cytoskeletal structures and promote cell motility. To explore the possibility that Cdk5 influences the Reelin pathway, we sought to determine whether Dab1 is a substrate for Cdk5. Here we show that Cdk5 phosphorylates Dab1 on serine 491 in vitro and in vivo, independently of Reelin signaling. We also show that ectopic neurons in Cdk5-deficient mice exhibit reduced levels of Reelin signaling during later stages of cortical development, although Cdk5 is not required for Reelin-induced tyrosine phosphorylation of Dab1. Although the functional significance of Dab1 serine phosphorylation is unclear, our results suggest that there is biochemical cross-talk between two signaling pathways that control cell positioning.
Key words: reeler; neuronal migration; Reelin; VLDLR; ApoER2; Dab1; Cdk5; p35; p39; phosphorylation; signal transduction
Copyright © 2002 Society for Neuroscience 0270-6474/02/22124869-09$05.00/0
This article has been cited by other articles:
T.-J. Park and T. Curran
Crk and Crk-Like Play Essential Overlapping Roles Downstream of Disabled-1 in the Reelin Pathway
J. Neurosci., December 10, 2008; 28(50): 13551 - 13562.
[Abstract] [Full Text] [PDF]
Y. Sato, M. Taoka, N. Sugiyama, K.-i. Kubo, T. Fuchigami, A. Asada, T. Saito, K. Nakajima, T. Isobe, and S.-i. Hisanaga
Regulation of the interaction of Disabled-1 with CIN85 by phosphorylation with Cyclin-dependent kinase 5.
Genes Cells, December 1, 2007; 12(12): 1315 - 1327.
[Abstract] [Full Text] [PDF]
T.-J. Park, K. Boyd, and T. Curran
Cardiovascular and Craniofacial Defects in Crk-Null Mice.
Mol. Cell. Biol., August 1, 2006; 26(16): 6272 - 6282.
[Abstract] [Full Text] [PDF]
C. J. Strock, J.-I. Park, E. K. Nakakura, G. S. Bova, J. T. Isaacs, D. W. Ball, and B. D. Nelkin
Cyclin-dependent kinase 5 activity controls cell motility and metastatic potential of prostate cancer cells.
Cancer Res., August 1, 2006; 66(15): 7509 - 7515.
[Abstract] [Full Text] [PDF]
A. Pramatarova, P. G. Ochalski, C.-H. Lee, and B. W. Howell
Mouse Disabled 1 Regulates the Nuclear Position of Neurons in a Drosophila Eye Model
Mol. Cell. Biol., February 15, 2006; 26(4): 1510 - 1517.
[Abstract] [Full Text] [PDF]
C. Gonzalez-Billault, J. A. Del Rio, J. M. Urena, E. M. Jimenez-Mateos, M. J. Barallobre, M. Pascual, L. Pujadas, S. Simo, A. L. Torre, R. Gavin, et al.
A role of MAP1B in Reelin-dependent Neuronal Migration
Cereb Cortex, August 1, 2005; 15(8): 1134 - 1145.
[Abstract] [Full Text] [PDF]
R. Homayouni, K. Heinrich, L. Wei, and M. W. Berry
Gene clustering by Latent Semantic Indexing of MEDLINE abstracts
Bioinformatics, January 1, 2005; 21(1): 104 - 115.
[Abstract] [Full Text] [PDF]
H. H. Bock, Y. Jossin, P. May, O. Bergner, and J. Herz
Apolipoprotein E Receptors Are Required for Reelin-induced Proteasomal Degradation of the Neuronal Adaptor Protein Disabled-1
J. Biol. Chem., August 6, 2004; 279(32): 33471 - 33479.
[Abstract] [Full Text] [PDF]
A. Louvi, S. S. Sisodia, and E. A. Grove
Presenilin 1 in migration and morphogenesis in the central nervous system
Development, July 1, 2004; 131(13): 3093 - 3105.
[Abstract] [Full Text] [PDF]
U. Beffert, E. J. Weeber, G. Morfini, J. Ko, S. T. Brady, L.-H. Tsai, J. D. Sweatt, and J. Herz
Reelin and Cyclin-Dependent Kinase 5-Dependent Signals Cooperate in Regulating Neuronal Migration and Synaptic Transmission
J. Neurosci., February 25, 2004; 24(8): 1897 - 1906.
[Abstract] [Full Text] [PDF]
V. Hammond, L.-H. Tsai, and S.-S. Tan
Control of Cortical Neuron Migration and Layering: Cell and Non Cell-Autonomous Effects of p35
J. Neurosci., January 14, 2004; 24(2): 576 - 587.
[Abstract] [Full Text] [PDF]
L. Arnaud, B. A. Ballif, and J. A. Cooper
Regulation of Protein Tyrosine Kinase Signaling by Substrate Degradation during Brain Development
Mol. Cell. Biol., December 15, 2003; 23(24): 9293 - 9302.
[Abstract] [Full Text] [PDF]
H. H. Bock, Y. Jossin, P. Liu, E. Forster, P. May, A. M. Goffinet, and J. Herz
Phosphatidylinositol 3-Kinase Interacts with the Adaptor Protein Dab1 in Response to Reelin Signaling and Is Required for Normal Cortical Lamination
J. Biol. Chem., October 3, 2003; 278(40): 38772 - 38779.
[Abstract] [Full Text] [PDF]
S. Kesavapany, K.-F. Lau, S. Ackerley, S. J. Banner, S. J. A. Shemilt, J. D. Cooper, P. N. Leigh, C. E. Shaw, D. M. McLoughlin, and C. C. J. Miller
Identification of a Novel, Membrane-Associated Neuronal Kinase, Cyclin-Dependent Kinase 5/p35-Regulated Kinase
J. Neurosci., June 15, 2003; 23(12): 4975 - 4983.
[Abstract] [Full Text] [PDF]
Y. Jossin, I. Bar, N. Ignatova, F. Tissir, C. L. de Rouvroit, and A. M. Goffinet
The Reelin Signaling Pathway: Some Recent Developments
Cereb Cortex, June 1, 2003; 13(6): 627 - 633.
[Abstract] [Full Text] [PDF]
H. Patzke, U. Maddineni, R. Ayala, M. Morabito, J. Volker, P. Dikkes, M. K. Ahlijanian, and L.-H. Tsai
Partial Rescue of the p35-/- Brain Phenotype by Low Expression of a Neuronal-Specific Enolase p25 Transgene
J. Neurosci., April 1, 2003; 23(7): 2769 - 2778.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|