| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, January 29, 1996, and in revised form, April 1, 1996)
From the Departments of Pathology, Anatomy & Cell Biology, and
§ Biochemistry & Molecular Biophysics, Columbia University
College of Physicians and Surgeons, New York, New York 10032
The high molecular weight neurofilament protein
(NF-H) is highly phosphorylated in the axon. The phosphorylation sites
have been identified as KSP (Lys-Ser-Pro) repeats in the tail domain of
NF-H. These KSP sequences are present more than 50 times in the NF-H
tail, and most of these sites are normally phosphorylated in
vivo. These KSP sites can be further divided into two separate
consensus sequences, KSPXK and KSPXY (where
Y is not K). The extensive phosphorylation of NF-H has been
proposed to play a critical role in the determination of axonal
diameter. Recent studies have shown that Cdk5, a kinase related to the
cell cycle-dependent kinase Cdc2, is expressed in the brain
and associates with the cytoskeleton. In vitro
phosphorylation studies have shown that Cdk5 in conjunction with its
activator, p35, is able to phosphorylate histone H1, dephosphorylated
NF-H, as well as a synthetic peptide with the repetitive KSP motif. We
have cloned the cDNAs for rat Cdk5 and p35 by reverse
transcription-polymerase chain reaction and cDNA library screening
and studied the phosphorylation of NF-H both in vivo and
in vitro. By transient transfection assays, we have shown
that NF-H can only be extensively phosphorylated in the presence of
both Cdk5 and p35. This phosphorylation can be inhibited by a
Cdk5-dominant negative mutant, an observation which further supports
that Cdk5 is a kinase that is able to phosphorylate NF-H. By
immunoprecipitating Cdk5 and p35 from the transfected cells, we have
been able to show that the KSPXK repeats are the preferred
phosphorylation sites for Cdk5, while the KSPXY repeats are
not directly phosphorylated by Cdk5 and p35.
Volume 271, Number 24,
Issue of June 14, 1996
pp. 14245-14251
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  P. Grant, Y. Zheng, and H. C. Pant Squid (Loligo pealei) Giant Fiber System: A Model for Studying Neurodegeneration and Dementia? Biol. Bull., June 1, 2006; 210(3): 318 - 333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ludemann, A. Clement, V. H. Hans, J. Leschik, C. Behl, and R. Brandt O-Glycosylation of the Tail Domain of Neurofilament Protein M in Human Neurons and in Spinal Cord Tissue of a Rat Model of Amyotrophic Lateral Sclerosis (ALS) J. Biol. Chem., September 9, 2005; 280(36): 31648 - 31658. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Bannerman, A. Hahn, S. Ramirez, M. Morley, C. Bonnemann, S. Yu, G.-X. Zhang, A. Rostami, and D. Pleasure Motor neuron pathology in experimental autoimmune encephalomyelitis: studies in THY1-YFP transgenic mice Brain, August 1, 2005; 128(8): 1877 - 1886. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. K.-H. Chan, A. Dickerson, D. Ortiz, A. F. Pimenta, C. M. Moran, J. Motil, S. J. Snyder, K. Malik, H. C. Pant, and T. B. Shea Mitogen-activated protein kinase regulates neurofilament axonal transport J. Cell Sci., September 15, 2004; 117(20): 4629 - 4642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Hirasawa, T. Ohshima, S. Takahashi, G. Longenecker, Y. Honjo, Veeranna, H. C. Pant, K. Mikoshiba, R. O. Brady, and A. B. Kulkarni Perinatal abrogation of Cdk5 expression in brain results in neuronal migration defects PNAS, April 20, 2004; 101(16): 6249 - 6254. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Khalili, L. Del Valle, V. Muralidharan, W. J. Gault, N. Darbinian, J. Otte, E. Meier, E. M. Johnson, D. C. Daniel, Y. Kinoshita, et al. Pur{alpha} Is Essential for Postnatal Brain Development and Developmentally Coupled Cellular Proliferation As Revealed by Genetic Inactivation in the Mouse Mol. Cell. Biol., October 1, 2003; 23(19): 6857 - 6875. [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]
|
|
|
|
 |
|
 S. Ackerley, P. Thornhill, A. J. Grierson, J. Brownlees, B. H. Anderton, P. N. Leigh, C. E. Shaw, and C. C.J. Miller Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments J. Cell Biol., May 12, 2003; 161(3): 489 - 495. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kashiwagi, B. Ou, S. Nakamura, Y. Tanaka, M. Suzuki, and S. Tsukahara Increase in Dephosphorylation of the Heavy Neurofilament Subunit in the Monkey Chronic Glaucoma Model Invest. Ophthalmol. Vis. Sci., January 1, 2003; 44(1): 154 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sasaki, M. Taoka, K. Ishiguro, A. Uchida, T. Saito, T. Isobe, and S.-i. Hisanaga In Vivo and in Vitro Phosphorylation at Ser-493 in the Glutamate (E)-segment of Neurofilament-H Subunit by Glycogen Synthase Kinase 3beta J. Biol. Chem., September 20, 2002; 277(39): 36032 - 36039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ko, S. Humbert, R. T. Bronson, S. Takahashi, A. B. Kulkarni, E. Li, and L.-H. Tsai p35 and p39 Are Essential for Cyclin-Dependent Kinase 5 Function during Neurodevelopment J. Neurosci., September 1, 2001; 21(17): 6758 - 6771. [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]
|
|
|
|
|
|
I. Sanchez, L. Hassinger, R. K. Sihag, D. W. Cleveland, P. Mohan, and R. A. Nixon Local Control of Neurofilament Accumulation during Radial Growth of Myelinating Axons In Vivo: Selective Role of Site-specific Phosphorylation J. Cell Biol., November 20, 2000; 151(5): 1013 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-S. Li, L. Zhang, J. Gu, N. D. Amin, and H. C. Pant Integrin alpha 1beta 1-Mediated Activation of Cyclin-Dependent Kinase 5 Activity Is Involved in Neurite Outgrowth and Human Neurofilament Protein H Lys-Ser-Pro Tail Domain Phosphorylation J. Neurosci., August 15, 2000; 20(16): 6055 - 6062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ackerley, A. J. Grierson, J. Brownlees, P. Thornhill, B. H. Anderton, P. N. Leigh, C. E. Shaw, and C. C.J. Miller Glutamate Slows Axonal Transport of Neurofilaments in Transfected Neurons J. Cell Biol., July 11, 2000; 150(1): 165 - 176. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takeda, T. Hatai, T. S. Hamazaki, H. Nishitoh, M. Saitoh, and H. Ichijo Apoptosis Signal-regulating Kinase 1 (ASK1) Induces Neuronal Differentiation and Survival of PC12 Cells J. Biol. Chem., March 24, 2000; 275(13): 9805 - 9813. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J Chen, T Nakata, Z Zhang, and N Hirokawa The C-terminal tail domain of neurofilament protein-H (NF-H) forms the crossbridges and regulates neurofilament bundle formation J. Cell Sci., January 11, 2000; 113(21): 3861 - 3869. [Abstract] [PDF]
|
|
|
|
|
|
H Tokuoka, T Saito, H Yorifuji, F Wei, T Kishimoto, and S Hisanaga Brain-derived neurotrophic factor-induced phosphorylation of neurofilament-H subunit in primary cultures of embryo rat cortical neurons J. Cell Sci., January 3, 2000; 113(6): 1059 - 1068. [Abstract] [PDF]
|
|
|
|
|
|
J Brownlees, A Yates, N. Bajaj, D Davis, B. Anderton, P. Leigh, C. Shaw, and C. Miller Phosphorylation of neurofilament heavy chain side-arms by stress activated protein kinase-1b/Jun N-terminal kinase-3 J. Cell Sci., January 2, 2000; 113(3): 401 - 407. [Abstract] [PDF]
|
|
|
|
|
|
G. Y. Ching, C.-L. Chien, R. Flores, and R. K. H. Liem Overexpression of alpha -Internexin Causes Abnormal Neurofilamentous Accumulations and Motor Coordination Deficits in Transgenic Mice J. Neurosci., April 15, 1999; 19(8): 2974 - 2986. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Veeranna, N. D. Amin, N. G. Ahn, H. Jaffe, C. A. Winters, P. Grant, and H. C. Pant Mitogen-Activated Protein Kinases (Erk1,2) Phosphorylate Lys-Ser-Pro (KSP) Repeats in Neurofilament Proteins NF-H and NF-M J. Neurosci., June 1, 1998; 18(11): 4008 - 4021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qi, D. Tang, X. Zhu, D. J. Fujita, and J. H. Wang Association of Neurofilament Proteins with Neuronal Cdk5 Activator J. Biol. Chem., January 23, 1998; 273(4): 2329 - 2335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. I. Giasson and W. E. Mushynski Study of Proline-Directed Protein Kinases Involved in Phosphorylation of the Heavy Neurofilament Subunit J. Neurosci., December 15, 1997; 17(24): 9466 - 9472. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Y.C. Poon, J. Lew, and T. Hunter Identification of Functional Domains in the Neuronal Cdk5 Activator Protein J. Biol. Chem., February 28, 1997; 272(9): 5703 - 5708. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sobue, A. Agarwal-Mawal, W. Li, W. Sun, Y. Miura, and H. K. Paudel Interaction of Neuronal Cdc2-like Protein Kinase with Microtubule-associated Protein Tau J. Biol. Chem., May 26, 2000; 275(22): 16673 - 16680. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. K. Ahlijanian, N. X. Barrezueta, R. D. Williams, A. Jakowski, K. P. Kowsz, S. McCarthy, T. Coskran, A. Carlo, P. A. Seymour, J. E. Burkhardt, et al. Hyperphosphorylated tau and neurofilament and cytoskeletal disruptions in mice overexpressing human p25, an activator of cdk5 PNAS, March 14, 2000; 97(6): 2910 - 2915. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
