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

J. Biol. Chem., Vol. 280, Issue 27, 25674-25686, July 8, 2005

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 280/27/25674    most recent M501332200v1 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 Rugg, M. S. Articles by Day, A. J. Search for Related Content PubMed PubMed Citation Articles by Rugg, M. S. Articles by Day, A. J. Social Bookmarking                      What's this?

Characterization of Complexes Formed between TSG-6 and Inter--inhibitor That Act as Intermediates in the Covalent Transfer of Heavy Chains onto Hyaluronan^*

Marilyn S. Rugg, Antony C. Willis, Durba Mukhopadhyay, Vincent C. Hascall, Erik Fries¶, Csaba Fülöp, Caroline M. Milner, and Anthony J. Day||

From the Medical Research Council Immunochemistry Unit, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom, the Section of Connective Tissue Biology, Department of Biomedical Engineering, Cleveland Clinic Foundation, Cleveland, Ohio 44195,, and the^¶ Department of Medical Biochemistry and Microbiology, Uppsala University, S-751 23 Uppsala, Sweden

The high molecular mass glycosaminoglycan hyaluronan (HA) can become modified by the covalent attachment of heavy chains (HCs) derived from the serum protein inter--inhibitor (II), which is composed of three subunits (HC1, HC2 and bikunin) linked together via a chondroitin sulfate moiety. The formation of HC·HA is likely to play an important role in the stabilization of HA-rich extracellular matrices in the context of inflammatory disease (e.g. arthritis) and ovulation. Here, we have characterized the complexes formed in vitro between purified human II and recombinant human TSG-6 (an inflammation-associated protein implicated previously in this process) and show that these complexes (i.e. TSG-6·HC1 and TSG-6·HC2) act as intermediates in the formation of HC·HA. This is likely to involve two transesterification reactions in which an ester bond linking an HC to chondroitin sulfate in intact II is transferred first onto TSG-6 and then onto HA. The formation of TSG-6·HC1 and TSG-6·HC2 complexes was accompanied by the production of bikunin·HC2 and bikunin·HC1 by-products, respectively, which were observed to break down, releasing free bikunin and HCs. Both TSG-6·HC formation and the subsequent HC transfer are metal ion-dependent processes; these reactions have a requirement for either Mg²⁺ or Mn²⁺ and are inhibited by Co²⁺. TSG-6, which is released upon the transfer of HCs from TSG-6 onto HA, was shown to combine with II to form new TSG-6·HC complexes and thus be recycled. The finding that TSG-6 acts as cofactor and catalyst in the production of HC·HA complexes has important implications for our understanding of inflammatory and inflammation-like processes.

Received for publication, February 4, 2005

^* This work was supported by the Medical Research Council and Arthritis Research Campaign Grants 16119 and 16539. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

This paper is dedicated to the memory of Professor Mike Bayliss, a friend and colleague who will be greatly missed.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Figs. S1–S4.

^|| To whom correspondence should be addressed. Tel.: 44-1865-275-349; Fax: 44-1865-275-729; E-mail: tony.day{at}bioch.ox.ac.uk.

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

This article has been cited by other articles:

				D. J. Mahoney, K. Mikecz, T. Ali, G. Mabilleau, D. Benayahu, A. Plaas, C. M. Milner, A. J. Day, and A. Sabokbar TSG-6 Regulates Bone Remodeling through Inhibition of Osteoblastogenesis and Osteoclast Activation J. Biol. Chem., September 19, 2008; 283(38): 25952 - 25962. [Abstract] [Full Text] [PDF]

				K. W. Sanggaard, C. S. Sonne-Schmidt, T. P. Krogager, K. A. Lorentzen, H.-G. Wisniewski, I. B. Thogersen, and J. J. Enghild The Transfer of Heavy Chains from Bikunin Proteins to Hyaluronan Requires Both TSG-6 and HC2 J. Biol. Chem., July 4, 2008; 283(27): 18530 - 18537. [Abstract] [Full Text] [PDF]

				E. Nagyova, A. Camaioni, R. Prochazka, A. J. Day, and A. Salustri Synthesis of Tumor Necrosis Factor Alpha-Induced Protein 6 in Porcine Preovulatory Follicles: A Study with A38 Antibody Biol Reprod, May 1, 2008; 78(5): 903 - 909. [Abstract] [Full Text] [PDF]

				L. Scarchilli, A. Camaioni, B. Bottazzi, V. Negri, A. Doni, L. Deban, A. Bastone, G. Salvatori, A. Mantovani, G. Siracusa, et al. PTX3 Interacts with Inter-{alpha}-trypsin Inhibitor: IMPLICATIONS FOR HYALURONAN ORGANIZATION AND CUMULUS OOPHORUS EXPANSION J. Biol. Chem., October 12, 2007; 282(41): 30161 - 30170. [Abstract] [Full Text] [PDF]

				C. D. Blundell, D. J. Mahoney, M. R. Cordell, A. Almond, J. D. Kahmann, A. Perczel, J. D. Taylor, I. D. Campbell, and A. J. Day Determining the Molecular Basis for the pH-dependent Interaction between the Link Module of Human TSG-6 and Hyaluronan J. Biol. Chem., April 27, 2007; 282(17): 12976 - 12988. [Abstract] [Full Text] [PDF]

				K. Sayasith, M. Dore, and J. Sirois Molecular characterization of tumor necrosis {alpha}-induced protein 6 and its human chorionic gonadotropin-dependent induction in theca and mural granulosa cells of equine preovulatory follicles Reproduction, January 1, 2007; 133(1): 135 - 145. [Abstract] [Full Text] [PDF]

				R. Forteza, S. M. Casalino-Matsuda, M. E. Monzon, E. Fries, M. S. Rugg, C. M. Milner, and A. J. Day TSG-6 Potentiates the Antitissue Kallikrein Activity of Inter-{alpha}-inhibitor through Bikunin Release Am. J. Respir. Cell Mol. Biol., January 1, 2007; 36(1): 20 - 31. [Abstract] [Full Text] [PDF]

				L. Zhuo, A. Kanamori, R. Kannagi, N. Itano, J. Wu, M. Hamaguchi, N. Ishiguro, and K. Kimata SHAP Potentiates the CD44-mediated Leukocyte Adhesion to the Hyaluronan Substratum J. Biol. Chem., July 21, 2006; 281(29): 20303 - 20314. [Abstract] [Full Text] [PDF]

				H. G Clarke, S. A Hope, S. Byers, and R. J Rodgers Formation of ovarian follicular fluid may be due to the osmotic potential of large glycosaminoglycans and proteoglycans Reproduction, July 1, 2006; 132(1): 119 - 131. [Abstract] [Full Text] [PDF]

				S. A. Kuznetsova, A. J. Day, D. J. Mahoney, M. S. Rugg, D. F. Mosher, and D. D. Roberts The N-terminal Module of Thrombospondin-1 Interacts with the Link Domain of TSG-6 and Enhances Its Covalent Association with the Heavy Chains of Inter-{alpha}-trypsin Inhibitor J. Biol. Chem., September 2, 2005; 280(35): 30899 - 30908. [Abstract] [Full Text] [PDF]

				D. J. Mahoney, B. Mulloy, M. J. Forster, C. D. Blundell, E. Fries, C. M Milner, and A. J. Day Characterization of the Interaction between Tumor Necrosis Factor-stimulated Gene-6 and Heparin: IMPLICATIONS FOR THE INHIBITION OF PLASMIN IN EXTRACELLULAR MATRIX MICROENVIRONMENTS J. Biol. Chem., July 22, 2005; 280(29): 27044 - 27055. [Abstract] [Full Text] [PDF]