HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lee, K.-Y. Articles by Wang, J. H. Search for Related Content PubMed PubMed Citation Articles by Lee, K.-Y. Articles by Wang, J. H. Social Bookmarking                      What's this?

Volume 272, Number 9, Issue of February 28, 1997 pp. 5622-5626
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

---

Neuronal Cdc2-like Kinase (Nclk) Binds and Phosphorylates the Retinoblastoma Protein

(Received for publication, December 2, 1996, and in revised form, December 24, 1996)

Ki-Young Lee , Caren C. Helbing ^¶ , Kyu-Sil Choi ^¶ , Randal N. Johnston ^¶ and Jerry H. Wang ^¶

From the Departments of  Anatomy and ^¶ Medical Biochemistry, The University of Calgary, Calgary, Alberta, Canada and the  Department of Biochemistry, The Hong Kong University of Science and Technology, Hong Kong

The tumor suppressor retinoblastoma protein (RB) plays a central role in cellular growth regulation, differentiation, and apoptosis. Phosphorylation of RB results in a consequent loss of its ability to inhibit cell cycle progression. However, how RB phosphorylation might be regulated in apoptotic or postmitotic cells, such as neurons, remains unclear. Here we report that neuronal Cdc2-like kinase (Nclk), composed of Cdk5 and a neuronal Cdk5 activator (p25^nck5a), can bind and phosphorylate RB. Since RB has been shown recently to associate with D-type G₁ cyclins and viral oncoproteins through a common peptide sequence motif of LXCXE, Nclk binding may be mediated by a related sequence motif (LXCXXE) found in p25^nck5a. We demonstrate (i) in vitro binding of bacterially expressed p25^nck5a to a GST-RB fusion protein, (ii) coprecipitation of GST-RB and reconstituted Cdk5·p25^nck5a, and (iii) phosphorylation of GST-RB by bacterially expressed Cdk5·p25^nck5a kinase and by Cdk5·p25^nck5a kinase purified from bovine brain. Finally, we show that immunoprecipitation of RB from embryonic mouse brain homogenate results in the coprecipitation of Cdk5 and that Cdk5 kinase activity is maximal during late embryonic development, a period when programmed cell death of developing neurons is greatest. Taken together, these results suggest that Nclk can bind to and phosphorylate RB in vitro and in vivo. We infer that Nclk may play an important role in regulating the activity of RB in the brain, including perhaps in apoptosing neurons.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S. Cicero and K. Herrup Cyclin-Dependent Kinase 5 Is Essential for Neuronal Cell Cycle Arrest and Differentiation J. Neurosci., October 19, 2005; 25(42): 9658 - 9668. [Abstract] [Full Text] [PDF]

				X. Tang, X. Wang, X. Gong, M. Tong, D. Park, Z. Xia, and Z. Mao Cyclin-Dependent Kinase 5 Mediates Neurotoxin-Induced Degradation of the Transcription Factor Myocyte Enhancer Factor 2 J. Neurosci., May 11, 2005; 25(19): 4823 - 4834. [Abstract] [Full Text] [PDF]

				M. Hamdane, A. Bretteville, A.-V. Sambo, K. Schindowski, S. Begard, A. Delacourte, P. Bertrand, and L. Buee p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death J. Cell Sci., March 15, 2005; 118(6): 1291 - 1298. [Abstract] [Full Text] [PDF]

				Z. Li, G. David, K.-W. Hung, R. A. DePinho, A. K. Y. Fu, and N. Y. Ip Cdk5/p35 Phosphorylates mSds3 and Regulates mSds3-mediated Repression of Transcription J. Biol. Chem., December 24, 2004; 279(52): 54438 - 54444. [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]

				M. D. Nguyen, M. Boudreau, J. Kriz, S. Couillard-Despres, D. R. Kaplan, and J.-P. Julien Cell Cycle Regulators in the Neuronal Death Pathway of Amyotrophic Lateral Sclerosis Caused by Mutant Superoxide Dismutase 1 J. Neurosci., March 15, 2003; 23(6): 2131 - 2140. [Abstract] [Full Text] [PDF]

				A. Catania, S. Urban, E. Yan, C. Hao, G. Barron, and J. Allalunis-Turner Expression and localization of cyclin-dependent kinase 5 in apoptotic human glioma cells Neuro-oncol, April 1, 2001; 3(2): 89 - 98. [Abstract] [PDF]

				H.-J. Liao, R. Kobayashi, and M. B. Mathews Activities of adenovirus virus-associated RNAs: Purification and characterization of RNA binding proteins PNAS, July 21, 1998; 95(15): 8514 - 8519. [Abstract] [Full Text] [PDF]

				X. Wang, Y.-P. Ching, W.-H. Lam, Z. Qi, M. Zhang, and J. H. Wang Identification of a Common Protein Association Region in the Neuronal Cdk5 Activator J. Biol. Chem., October 6, 2000; 275(41): 31763 - 31769. [Abstract] [Full Text] [PDF]