2011
DOI: 10.1074/jbc.m111.228114
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A Systems Biology Approach for the Investigation of the Heparin/Heparan Sulfate Interactome

Abstract: A large body of evidence supports the involvement of heparan sulfate (HS) proteoglycans in physiological processes such as development and diseases including cancer and neurodegenerative disorders. The role of HS emerges from its ability to interact and regulate the activity of a vast number of extracellular proteins including growth factors and extracellular matrix components. A global view on how protein-HS interactions influence the extracellular proteome and, consequently, cell function is currently lackin… Show more

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Cited by 222 publications
(248 citation statements)
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“…Heparan sulfate-like glycosaminoglycans have been biochemically identified in phyla at the base of the metazoan lineage such as Cnidaria (60). Intriguingly, the choanoflagellate Monosiga brevicollis presents, although with low homologies, ortholog sequences to key heparan sulfate biosynthetic enzymes (61). Although heparan sulfate has not been thus far identified in sponges, the rudimentary biosynthetic machinery present in their putative single-celled ancestor possibly participated as a precursor of the enzymes involved in the synthesis of their own sulfated polysaccharides.…”
Section: Discussionmentioning
confidence: 99%
“…Heparan sulfate-like glycosaminoglycans have been biochemically identified in phyla at the base of the metazoan lineage such as Cnidaria (60). Intriguingly, the choanoflagellate Monosiga brevicollis presents, although with low homologies, ortholog sequences to key heparan sulfate biosynthetic enzymes (61). Although heparan sulfate has not been thus far identified in sponges, the rudimentary biosynthetic machinery present in their putative single-celled ancestor possibly participated as a precursor of the enzymes involved in the synthesis of their own sulfated polysaccharides.…”
Section: Discussionmentioning
confidence: 99%
“…HS chains are dominant molecules in the pericellular matrix surrounding the plasma membrane and can bind to a broad range of ligands, 14,15 thereby HSPGs can mediate extracellular transportation of several morphogens and growth factors. Extracellular diffusion of Wnt and Hedgehog, which are important players in heart development, can be hindered by noncovalent binding to cell surface HSPGs.…”
Section: Nonstructural Ecm Proteins and Extracellular Transportation mentioning
confidence: 99%
“…12,13 The authors, therefore, hypothesized that these proteins could be efficiently incorporated into preformed DSCS NPs. There are more than 435 heparinbinding proteins in humans, 14 including many growth factors and cytokines. The authors chose five such proteins for this study whose three-dimensional structures and/or interactions with heparin have been well documented.…”
Section: Introductionmentioning
confidence: 99%