Characterization of the high affinity cell-binding domain in the cell surface proteoglycan syndecan-4.
The syndecan family of cell surface proteoglycans regulates cell adhesion via their glycosaminoglycan chains and discrete domains of their core proteins. Core protein domains that are variable between syndecan family members may regulate syndecan-specific associations, thereby endowing individual syndecans with unique functions. A syndecan-4-specific domain has been identified in the extracellular syndecan-4 protein. This region mediates cell adhesion when provided as an artificial substratum and is localized within amino acids 56-109 of the recombinant extracellular protein domain of mouse syndecan-4 (mS4ED) (McFall, A. J., and Rapraeger, A. C. (1997) J. Biol. Chem. 272, 12901-12904). To characterize its interaction with the cell surface, radiolabeled ligand binding studies were performed. A single high affinity interaction, with a dissociation constant of 2 x 10(-9) M, was observed between mS4ED and both human and mouse cells. Both chicken S4ED and mS4ED compete for this interaction, although they are only 34% identical within the cell-binding domain sequence. The extracellular protein domains of syndecan-1, -2, and -3, however, fail to compete. The interaction is also observed with native syndecan-4 shed from cell surfaces. Interestingly, the extracellular protein domain of syndecan-1 also mediates cell adhesion, suggesting a similar but discrete interaction for this family member.
Program in Cellular and Molecular Biology and Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, Wisconsin 53706-1532, USA.
A J
AJ
McFall
A C
AC
Rapraeger
D000818:Animals; D001665:Binding Sites; D002413:Cations, Divalent; D002448:Cell Adhesion; D002645:Chickens; D004730:Endothelium, Vascular; D005347:Fibroblasts; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D011485:Protein Binding; D011509:Proteoglycans / Q000378:metabolism*; D011869:Radioligand Assay; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans
D002413:Cations, Divalent; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D011509:Proteoglycans; C508241:SDC1 protein, human; C508304:SDC4 protein, human; C508242:Sdc1 protein, mouse; C508306:Sdc4 protein, mouse; D053668:Syndecan-1; D053671:Syndecan-4; D053667:Syndecans