Glycobiology Advance Access originally published online on October 30, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Glycobiology, 2003, Vol. 13, No. 1 35-42
© 2003 Oxford University Press
Glycosaminoglycan structures required for strong binding to midkine, a heparin-binding growth factor
2 Department of Biochemistry, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan
3 Department of Life Science, Aichi University of Education, Kariya, Aichi 448-8542, Japan
4 Meiji Dairies Corporation, 540 Naruda, Odawara 250-0862, Japan
Received on July 22, 2002; revised on August 16, 2002; accepted on August 18, 2002
Midkine (MK), a heparin-binding growth factor, binds strongly to oversulfated structures in chondroitin sulfates (CSs) and heparan sulfate. To elucidate the carbohydrate structure actually involved in the strong binding, dissected brains from 13-day mouse embryos were incubated with [14C]-glucosamine. The labeled glycosaminoglycans were fractionated by MK-agarose affinity chromatography to a weakly binding fraction, which was eluted by 0.5 M NaCl, and a strongly binding fraction, which was eluted by higher NaCl concentrations. Among the unsaturated disaccharides released from the strongly binding fraction by chondroitinase ABC, 
Di-diSE with 4,6-disulfated N-acetylgalactosamine accounted for 32.3%, whereas its content was lower in the weakly binding fraction. Artificial CS-E structure was formed using N-acetylgalactosamine 4-sulfate 6-O-sulfotransferase purified from squid or recombinant human enzyme. Analysis of the products and their interaction with MK revealed that E units without 3-O-sulfation of glucuronic acid are sufficient for strong binding, provided that they are present as a dense cluster. Among the sulfated disaccharides released by heparitinase digestion, the trisulfated one, DiHS-triS, was the most abundant in the strongly binding fraction and was lower in the weakly binding fraction. Together with results of previous studies, we concluded that the multivalent trisulfated heparin-like unit is another structure involved in strong binding to MK.
1 To whom correspondence should be addressed; e-mail: tmurama{at}med.nagoya-u.ac.jp
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Ishii and N. Maeda Spatiotemporal expression of chondroitin sulfate sulfotransferases in the postnatal developing mouse cerebellum Glycobiology, August 1, 2008; 18(8): 602 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Akita, A. von Holst, Y. Furukawa, T. Mikami, K. Sugahara, and A. Faissner Expression of Multiple Chondroitin/Dermatan Sulfotransferases in the Neurogenic Regions of the Embryonic and Adult Central Nervous System Implies That Complex Chondroitin Sulfates Have a Role in Neural Stem Cell Maintenance Stem Cells, March 1, 2008; 26(3): 798 - 809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Purushothaman, J. Fukuda, S. Mizumoto, G. B. ten Dam, T. H. van Kuppevelt, H. Kitagawa, T. Mikami, and K. Sugahara Functions of Chondroitin Sulfate/Dermatan Sulfate Chains in Brain Development: CRITICAL ROLES OF E AND iE DISACCHARIDE UNITS RECOGNIZED BY A SINGLE CHAIN ANTIBODY GD3G7 J. Biol. Chem., July 6, 2007; 282(27): 19442 - 19452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ichihara-Tanaka, A. Oohira, M. Rumsby, and T. Muramatsu Neuroglycan C Is a Novel Midkine Receptor Involved in Process Elongation of Oligodendroglial Precursor-like Cells J. Biol. Chem., October 13, 2006; 281(41): 30857 - 30864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ida, T. Shuo, K. Hirano, Y. Tokita, K. Nakanishi, F. Matsui, S. Aono, H. Fujita, Y. Fujiwara, T. Kaji, et al. Identification and Functions of Chondroitin Sulfate in the Milieu of Neural Stem Cells J. Biol. Chem., March 3, 2006; 281(9): 5982 - 5991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Maeda, N. Fukazawa, and T. Hata The Binding of Chondroitin Sulfate to Pleiotrophin/Heparin-binding Growth-associated Molecule Is Regulated by Chain Length and Oversulfated Structures J. Biol. Chem., February 24, 2006; 281(8): 4894 - 4902. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ohtake, K. Kimata, and O. Habuchi Recognition of Sulfation Pattern of Chondroitin Sulfate by Uronosyl 2-O-Sulfotransferase J. Biol. Chem., November 25, 2005; 280(47): 39115 - 39123. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ito, M. Hikino, Y. Yajima, T. Mikami, S. Sirko, A. von Holst, A. Faissner, S. Fukui, and K. Sugahara Structural characterization of the epitopes of the monoclonal antibodies 473HD, CS-56, and MO-225 specific for chondroitin sulfate D-type using the oligosaccharide library Glycobiology, June 1, 2005; 15(6): 593 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Bao, S. Nishimura, T. Mikami, S. Yamada, N. Itoh, and K. Sugahara Chondroitin Sulfate/Dermatan Sulfate Hybrid Chains from Embryonic Pig Brain, Which Contain a Higher Proportion of L-Iduronic Acid than Those from Adult Pig Brain, Exhibit Neuritogenic and Growth Factor Binding Activities J. Biol. Chem., March 12, 2004; 279(11): 9765 - 9776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Hikino, T. Mikami, A. Faissner, A.-C. E. S. Vilela-Silva, M. S. G. Pavao, and K. Sugahara Oversulfated Dermatan Sulfate Exhibits Neurite Outgrowth-promoting Activity toward Embryonic Mouse Hippocampal Neurons: IMPLICATIONS OF DERMATAN SULFATE IN NEURITOGENESIS IN THE BRAIN J. Biol. Chem., October 31, 2003; 278(44): 43744 - 43754. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Maeda, J. He, Y. Yajima, T. Mikami, K. Sugahara, and T. Yabe Heterogeneity of the Chondroitin Sulfate Portion of Phosphacan/6B4 Proteoglycan Regulates Its Binding Affinity for Pleiotrophin/Heparin Binding Growth-associated Molecule J. Biol. Chem., September 12, 2003; 278(37): 35805 - 35811. [Abstract] [Full Text] [PDF]
|
|