Recombinant Mouse Syndecan-4 Protein, CF

Syndecan-4, previously known as amphiglycan or ryudocan, is a member of the syndecan family of type 1 transmembrane proteins capable of carrying heparan sulfate (HS) and chondroitin sulfate glycosaminoglycans (1 ‑ 4). The four vertebrate syndecans have two conserved cytoplasmic domains and divergent extracellular portions, except for HS attachment sites. Syndecan-4 is the most similar to Syndecan-2, but is more universally expressed and is found in virtually every cell type. Expression can be up‑regulated by TGF-beta 2 and in response to mechanical stress in smooth muscle, wound healing, arterial injury or acute myocardial infarction, probably in response to at least one inflammatory mediator (1, 2). Mouse Syndecan-4 is synthesized as a 198 amino acid (aa) core protein with a 22 aa signal sequence, a 123 aa extracellular domain containing three consensus Ser-Gly sequences for the attachment of HS side chains and a conserved NXIP (X = any aa) cell adhesion site, a 25 aa transmembrane region and a 28 aa cytoplasmic tail (3 - 5). Mouse Syndecan-4 ECD shares approximately 79%, 91%, 79%, 77%, 77% and 75% aa identity with human, rat, canine, bovine, equine and porcine Syndecan-4 ECD, respectively. Addition of 20 - 80 disaccharides per side chain adds considerably to the size of the 20 kDa core protein. Non-covalent homodimerization of Syndecan-4 is dependent on the transmembrane domain (6). The HS chains can bind fibronectin, SDF-1, antithrombin, FGF-2, midkine and tissue factor pathway inhibitor and can present FGF-2 to its receptors (1, 2, 7). The NXIP site is critical for integrin-dependent binding of mesenchymal cells or vascular endothelium (5). Proteolytic cleavage by plasmin, thrombin or a metalloproteinase may create a functional ectodomain (8 - 10). Genetic disruption of the Syndecan-4 gene causes a mild phenotype, presumably due to compensation by other syndecans, but mice have an increase in placental thrombi as well as defects in wound healing and response to endotoxin shock (11, 12).