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Biglycan isoforms with differences in polysaccharide substitution and core protein in human lung fibroblasts.

Tufvesson, Ellen LU ; Malmström, Johan LU ; Marko-Varga, György LU and Westergren-Thorsson, Gunilla LU (2002) In European Journal of Biochemistry 269(15). p.3688-3696
Abstract
Biglycan is widely distributed in the extracellular matrix and is a member of the small proteoglycan family characterized by a core protein with leucine-rich repeat motifs. We show in this paper for the first time that biglycan from human lung fibroblasts can be expressed as different isoforms. These isoforms can be separated from the predominant form of biglycan by hydrophobic interaction chromatography, where the more hydrophobic isoforms are retarded. The newly found isoforms of biglycan have a smaller core protein substituted with smaller glycosaminoglycan chains, migrating on SDS/PAGE at between 110 and 200 kDa. These molecules were identified as biglycan using MALDI-TOF MS. Identification of C-terminal peptides together with... (More)
Biglycan is widely distributed in the extracellular matrix and is a member of the small proteoglycan family characterized by a core protein with leucine-rich repeat motifs. We show in this paper for the first time that biglycan from human lung fibroblasts can be expressed as different isoforms. These isoforms can be separated from the predominant form of biglycan by hydrophobic interaction chromatography, where the more hydrophobic isoforms are retarded. The newly found isoforms of biglycan have a smaller core protein substituted with smaller glycosaminoglycan chains, migrating on SDS/PAGE at between 110 and 200 kDa. These molecules were identified as biglycan using MALDI-TOF MS. Identification of C-terminal peptides together with glycosylation of the N-terminal glycosaminoglycan sites excludes the possibility of terminal proteolytic cleavage. The biglycan isoforms are N-glycosylated, which demonstrates that a lack in N-glycosylation is not the reason for a smaller core. Two components revealed by RT-PCR indicate alternative splicing, which could be located in regions of the protein that have not been identified, with the exclusion of sites of glycosylations. Analyses of glycosaminoglycan chain length of the isoforms show that besides the normally occurring glycosaminoglycan chains, there is a mixture of shorter glycosaminoglycan chains. Structural analysis shows that these glycosaminoglycan chains contain a lower proportion of iduronic acid (61%) relative to glucuronic acid when compared to the glycosaminoglycan chain of the predominant form of biglycan (71%). We can anticipate that variation in structure of biglycan can cause changes in the connective tissue formation depending on its ability to bind matrix molecules, as well as cytokines. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
European Journal of Biochemistry
volume
269
issue
15
pages
3688 - 3696
publisher
Wiley-Blackwell
external identifiers
  • pmid:12153565
  • wos:000177782100009
  • scopus:0036359160
ISSN
0014-2956
DOI
10.1046/j.1432-1033.2002.03058.x
language
English
LU publication?
yes
id
8806752b-ace9-4591-8d28-c0e0e0e59d82 (old id 109722)
date added to LUP
2007-06-28 09:27:40
date last changed
2017-01-01 07:25:21
@article{8806752b-ace9-4591-8d28-c0e0e0e59d82,
  abstract     = {Biglycan is widely distributed in the extracellular matrix and is a member of the small proteoglycan family characterized by a core protein with leucine-rich repeat motifs. We show in this paper for the first time that biglycan from human lung fibroblasts can be expressed as different isoforms. These isoforms can be separated from the predominant form of biglycan by hydrophobic interaction chromatography, where the more hydrophobic isoforms are retarded. The newly found isoforms of biglycan have a smaller core protein substituted with smaller glycosaminoglycan chains, migrating on SDS/PAGE at between 110 and 200 kDa. These molecules were identified as biglycan using MALDI-TOF MS. Identification of C-terminal peptides together with glycosylation of the N-terminal glycosaminoglycan sites excludes the possibility of terminal proteolytic cleavage. The biglycan isoforms are N-glycosylated, which demonstrates that a lack in N-glycosylation is not the reason for a smaller core. Two components revealed by RT-PCR indicate alternative splicing, which could be located in regions of the protein that have not been identified, with the exclusion of sites of glycosylations. Analyses of glycosaminoglycan chain length of the isoforms show that besides the normally occurring glycosaminoglycan chains, there is a mixture of shorter glycosaminoglycan chains. Structural analysis shows that these glycosaminoglycan chains contain a lower proportion of iduronic acid (61%) relative to glucuronic acid when compared to the glycosaminoglycan chain of the predominant form of biglycan (71%). We can anticipate that variation in structure of biglycan can cause changes in the connective tissue formation depending on its ability to bind matrix molecules, as well as cytokines.},
  author       = {Tufvesson, Ellen and Malmström, Johan and Marko-Varga, György and Westergren-Thorsson, Gunilla},
  issn         = {0014-2956},
  language     = {eng},
  number       = {15},
  pages        = {3688--3696},
  publisher    = {Wiley-Blackwell},
  series       = {European Journal of Biochemistry},
  title        = {Biglycan isoforms with differences in polysaccharide substitution and core protein in human lung fibroblasts.},
  url          = {http://dx.doi.org/10.1046/j.1432-1033.2002.03058.x},
  volume       = {269},
  year         = {2002},
}