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The FASEB Journal, Vol 6, 861-870, Copyright © 1992 by The Federation of American Societies for Experimental Biology

REVIEWS

Proteoglycans: many forms and many functions

TE Hardingham and AJ Fosang
Biochemistry Division, Kennedy Institute, Hammersmith, London, United Kingdom.

Proteoglycans are produced by most eukaryotic cells and are versatile components of pericellular and extracellular matrices. They belong to many different protein families. Their functions vary from the physical effects of the proteoglycan aggrecan, which binds with link protein to hyaluronan to form multimolecular aggregates in cartilage; to the intercalated membrane protein CD44 that has a proteoglycan form and is a receptor and a cell-binding site for hyaluronan; to heparan sulfate proteoglycans of the syndecan and other families that provide matrix binding sites and cell-surface receptors for growth factors such as fibroblast growth factor (FGF). One feature that recurs in proteoglycan biology is that their structure is open to extensive modulation during cellular expression. Examples of protein changes are known, but a major source of structural variation is in the glycosaminoglycan chains. The number of chains and their length can vary, as well as their pattern of sulfation. This may result in the switching of different chain types with different properties, e.g., chondroitin sulfate and heparan sulfate, and it may also result in the selective expression of sulfated chain sequences that have specific functions. The control of glycosaminoglycan structure is not well understood, but it does appear to be used to change the properties of proteoglycans to suit different biological needs. Proteoglycan forms of proteins are thus important modifiers of the organization of the pericellular and extracellular matrices and modulators of the processes that occur there.


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J. HUANG, R. OLIVENSTEIN, R. TAHA, Q. HAMID, and M. LUDWIG
Enhanced Proteoglycan Deposition in the Airway Wall of Atopic Asthmatics
Am. J. Respir. Crit. Care Med., August 1, 1999; 160(2): 725 - 729.
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E. M Culav, C H. Clark, and M. J Merrilees
Connective Tissues: Matrix Composition and Its Relevance to Physical Therapy
Physical Therapy, March 1, 1999; 79(3): 308 - 319.
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S. F. Penc, B. Pomahac, T. Winkler, R. A. Dorschner, E. Eriksson, M. Herndon, and R. L. Gallo
Dermatan Sulfate Released after Injury Is a Potent Promoter of Fibroblast Growth Factor-2 Function
J. Biol. Chem., October 23, 1998; 273(43): 28116 - 28121.
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 Am. J. Respir. Cell Mol. Bio.Home page
M. Dolhnikoff, J. Morin, P. J. Roughley, and M. S. Ludwig
Expression of Lumican in Human Lungs
Am. J. Respir. Cell Mol. Biol., October 1, 1998; 19(4): 582 - 587.
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W. Halfter, S. Dong, B. Schurer, and G. J. Cole
Collagen XVIII Is a Basement Membrane Heparan Sulfate Proteoglycan
J. Biol. Chem., September 25, 1998; 273(39): 25404 - 25412.
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C. J. Ianelli, R. DeLellis, and D. A. Thorley-Lawson
CD48 Binds to Heparan Sulfate on the Surface of Epithelial Cells
J. Biol. Chem., September 4, 1998; 273(36): 23367 - 23375.
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H. Satoh, M. Susaki, C. Shukunami, K.-i. Iyama, T. Negoro, and Y. Hiraki
Functional Analysis of Diastrophic Dysplasia Sulfate Transporter. ITS INVOLVEMENT IN GROWTH REGULATION OF CHONDROCYTES MEDIATED BY SULFATED PROTEOGLYCANS
J. Biol. Chem., May 15, 1998; 273(20): 12307 - 12315.
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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
D. Negrini, A. Passi, G. De Luca, and G. Miserocchi
Proteoglycan involvement during development of lesional pulmonary edema
Am J Physiol Lung Cell Mol Physiol, February 1, 1998; 274(2): L203 - L211.
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 CROBMHome page
M.M. Klinger, F. Rahemtulla, C.W. Prince, L.C. Lucas, and J.E. Lemons
Proteoglycans At the Bone-Implant Interface
Critical Reviews in Oral Biology & Medicine, January 1, 1998; 9(4): 449 - 463.
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C. Lander, H. Zhang, and S. Hockfield
Neurons Produce a Neuronal Cell Surface-Associated Chondroitin Sulfate Proteoglycan
J. Neurosci., January 1, 1998; 18(1): 174 - 183.
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 JDRHome page
S. Yamauchi, H. Cheng, P. Neame, B. Caterson, and M. Yamauchi
Identification, Partial Characterization, and Distribution of Versican and Link Protein in Bovine Dental Pulp
Journal of Dental Research, November 1, 1997; 76(11): 1730 - 1736.
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H. Watanabe, S. C. Cheung, N. Itano, K. Kimata, and Y. Yamada
Identification of Hyaluronan-binding Domains of Aggrecan
J. Biol. Chem., October 31, 1997; 272(44): 28057 - 28065.
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W. Lin, S. Shuster, H. I. Maibach, and R. Stern
Patterns of Hyaluronan Staining Are Modified by Fixation Techniques
J. Histochem. Cytochem., August 1, 1997; 45(8): 1157 - 1164.
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 Proc. Natl. Acad. Sci. USAHome page
H. Watanabe, K. Nakata, K. Kimata, I. Nakanishi, and Y. Yamada
Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan
PNAS, June 24, 1997; 94(13): 6943 - 6947.
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S. Pillarisetti, L. Paka, A. Sasaki, T. Vanni-Reyes, B. Yin, N. Parthasarathy, W. D. Wagner, and I. J. Goldberg
Endothelial Cell Heparanase Modulation of Lipoprotein Lipase Activity. EVIDENCE THAT HEPARAN SULFATE OLIGOSACCHARIDE IS AN EXTRACELLULAR CHAPERONE
J. Biol. Chem., June 20, 1997; 272(25): 15753 - 15759.
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O. Oksala, K. Haapasalmi, L. Hakkinen, V.-J. Uitto, and H. Larjava
Expression of Heparan Sulphate and Small Dermatan/Chondroitin Sulphate Proteoglycans in Chronically Inflamed Human Periodontium
Journal of Dental Research, June 1, 1997; 76(6): 1250 - 1259.
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D. Bonneh-Barkay, M. Shlissel, B. Berman, E. Shaoul, A. Admon, I. Vlodavsky, D. J. Carey, V. K. Asundi, R. Reich-Slotky, and D. Ron
Identification of Glypican as a Dual Modulator of the Biological Activity of Fibroblast Growth Factors
J. Biol. Chem., May 9, 1997; 272(19): 12415 - 12421.
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C. Lander, P. Kind, M. Maleski, and S. Hockfield
A Family of Activity-Dependent Neuronal Cell-Surface Chondroitin Sulfate Proteoglycans in Cat Visual Cortex
J. Neurosci., March 15, 1997; 17(6): 1928 - 1939.
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N. Hauser, M. Paulsson, D. Heinegard, and M. Morgelin
Interaction of Cartilage Matrix Protein with Aggrecan. INCREASED COVALENT CROSS-LINKING WITH TISSUE MATURATION
J. Biol. Chem., December 13, 1996; 271(50): 32247 - 32252.
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W. Luo, T. S. Kuwada, L. Chandrasekaran, J. Zheng, and M. L. Tanzer
Divergent Secretory Behavior of the Opposite Ends of Aggrecan
J. Biol. Chem., July 12, 1996; 271(28): 16447 - 16450.
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Y. S. Kim, Y. Y. Jo, I. M. Chang, T. Toida, Y. Park, and R. J. Linhardt
A New Glycosaminoglycan from the Giant African Snail Achatina fulica
J. Biol. Chem., May 17, 1996; 271(20): 11750 - 11755.
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H. Kobayashi, J. Gotoh, Y. Hirashima, and T. Terao
Inter-alpha-trypsin Inhibitor Bound to Tumor Cells Is Cleaved into the Heavy Chains and the Light Chain on the Cell Surface
J. Biol. Chem., May 10, 1996; 271(19): 11362 - 11367.
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C.Z. Zhang, H. Li, P.M. Bartold, W.G. Young, and M.J. Waters
Effect of Growth Hormone on the Distribution of Decorin and Biglycan during Odontogenesis in the Rat Incisor
Journal of Dental Research, October 1, 1995; 74(10): 1636 - 1643.
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J. Grover, X.-N. Chen, J. R. Korenberg, and P. J. Roughley
The Human Lumican Gene
J. Biol. Chem., September 15, 1995; 270(37): 21942 - 21949.
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M. Buschmann, Y. Gluzband, A. Grodzinsky, and E. Hunziker
Mechanical compression modulates matrix biosynthesis in chondrocyte/agarose culture
J. Cell Sci., January 4, 1995; 108(4): 1497 - 1508.
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G Huet, I Kim, C de Bolos, J. Lo-Guidice, O Moreau, B Hemon, C Richet, P Delannoy, F. Real, and P Degand
Characterization of mucins and proteoglycans synthesized by a mucin-secreting HT-29 cell subpopulation
J. Cell Sci., January 3, 1995; 108(3): 1275 - 1285.
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 CROBMHome page
C. N. Bertolami and D. V. Messadi
The Role of Proteoglycans in Hard and Soft Tissue Repair
Critical Reviews in Oral Biology & Medicine, January 1, 1994; 5(3): 311 - 337.
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A. Faassen, D. Mooradian, R. Tranquillo, R. Dickinson, P. Letourneau, T. Oegema, and J. McCarthy
Cell surface CD44-related chondroitin sulfate proteoglycan is required for transforming growth factor-beta-stimulated mouse melanoma cell motility and invasive behavior on type I collagen
J. Cell Sci., January 6, 1993; 105(2): 501 - 511.
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J. Adams and F. Watt
Regulation of development and differentiation by the extracellular matrix
Development, January 4, 1993; 117(4): 1183 - 1198.
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B. Vertel, L. Walters, B Grier, N Maine, and P. Goetinck
Nanomelic chondrocytes synthesize, but fail to translocate, a truncated aggrecan precursor
J. Cell Sci., January 3, 1993; 104(3): 939 - 948.
[Abstract] [PDF]

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 Journal of Bioactive and Compatible PolymersHome page
M. Mattioli Belmonte, G. Biagini, G. Ricotti, C. Zucchini, C. Castaldini, M. Fini, R. Giardino, and M. Bigini
Experimental Wound Dressing by Heterologous Collagen: A Morphological-Quantitative Approach
Journal of Bioactive and Compatible Polymers, January 1, 1993; 8(4): 365 - 382.
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 J. Biol. Chem.Home page
P. L. DeAngelis and A. J. Padgett-McCue
Identification and Molecular Cloning of a Chondroitin Synthase from Pasteurella multocida Type F
J. Biol. Chem., July 28, 2000; 275(31): 24124 - 24129.
[Abstract] [Full Text] [PDF]


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