Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.2.2.7 (heparinase)
 1,270 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The heparan sulfate proteoglycan (HSPGs) is a components of the extracellular matrix of skeletal muscle that is concentrated at the neuromuscular junction (NMJ). Recent studies have suggested that HSPG, together with its bound peptide growth factors, plays important roles in autocrine or paracrine types of regulation of cell growth and differentiation. Heparin-binding growth-associated molecule (HB-GAM; also known as pleiotrophin, or p18) is a newly discovered HSPG-bound factor that is expressed at high levels in the developing CNS and PNS. In this study, we examined the role of this factor in NMJ development by examining its relationship to the formation of ACh receptor (AChR) clusters. Using an antibody against recombinant rat brain HB-GAM, we found that this protein is present prominently on the surface of cultured Xenopus myotomal muscle cells by immunocytochemistry. It is associated with HSPGs as evidenced by the fact that heparin and heparinase treatment greatly diminished the antibody labeling. HB-GAM is concentrated at preexisting AChR hot spots as well as at those induced by polystyrene beads. In addition, this molecule is also concentrated at AChR clusters induced by spinal cord neurons in nerve-muscle cocultures. To assess its function in synaptic induction, we applied recombinant HB-GAM-coated beads to cultured muscle cells to effect its focal presentation. Over 70% of these beads induced the formation of AChR clusters as shown by fluorescent alpha-bungarotoxin labeling. Furthermore, bath application of HB-GAM inhibited the nerve-induced formation of AChR clusters. Thus, HB-GAM is an endogenous muscle-derived factor that may be a component of the molecular mechanism in postsynaptic induction.
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PMID:The role of heparin-binding growth-associated molecule (HB-GAM) in the postsynaptic induction in cultured muscle cells. 772 43

OSF-1/HB-GAM is a member of developmentally regulated growth factors and cytokines. High expression levels of this factor are found in different tissues, e.g., in brain and in bone. We have analyzed the biological function and binding properties of natural OSF-1 to human osteoblasts. Using antibodies raised against the entire OSF-1 molecule or a synthetic carboxy-terminal peptide (amino acids (aa) 110-140) we have investigated the binding sites of rat OSF-1 on human osteoblast-like osteosarcoma cell lines: HOS(TE85) and MG-63. Immunofluorescence microscopic studies and flow cytometric data revealed that OSF-1 is specifically bound to the surface of these cells. Further characterization of the binding sites showed that both osteosarcoma cells express two different kinds of binding sites: Besides binding to a specific OSF-1 receptor, OSF-1 also significantly binds to cell surface heparan sulfates. Using the peptide specific polyclonal antibody we show that the carboxy-terminal domain, aa 110 to 140 of OSF-1, seems to be involved in ligand binding. Studies on the biological function of OSF-1 revealed a strong cell attachment promoting activity in vitro. This activity is not diminished after digestion of cell surface heparan sulfates by heparinase I and heparitinase I, demonstrating that the OSF-1 receptor mediates the cell attachment of osteoblasts. Our results indicate that one biological function of OSF-1 is the promotion of osteoblast attachment to the extracellular bone matrix.
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PMID:Receptor binding of osteoblast-specific factor 1 (OSF-1/HB-GAM) to human osteosarcoma cells promotes cell attachment. 792 91