Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.6.4 (chondroitinase)
 2,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Midkine, a heparin-binding growth factor, plays a critical role in cell migration causing suppression of neointima formation in midkine-deficient mice. Here we have determined the molecules essential for midkine-induced migration. Midkine induced haptotaxis of osteoblast-like cells, which was abrogated by the soluble form of midkine or pleiotrophin, a midkine-homologous protein. Chondroitin sulfate B, E, chondroitinase ABC, B, and orthovanadate, an inhibitor of protein-tyrosine phosphatase, suppressed the migration. Supporting these data, the cells examined expressed PTPzeta, a receptor-type protein-tyrosine phosphatase that exhibits high affinity to both midkine and pleiotrophin and harbors chondroitin sulfate chains. Furthermore, strong synergism between midkine and platelet-derived growth factor in migration was detected. The use of specific inhibitors demonstrated that mitogen-activated protein (MAP) kinase and protein-tyrosine phosphatase were involved in midkine-induced haptotaxis but not PDGF-induced chemotaxis, whereas phosphatidylinositol 3 (PI3)-kinase and protein kinase C were involved in both functions. Midkine activated both PI3-kinase and MAP kinases, the latter activation was blocked by a PI3-kinase inhibitor. Midkine further recruited PTPzeta and PI3-kinase. These results indicate that PTPzeta and concerted signaling involving PI3-kinase and MAP kinase are required for midkine-induced migration and demonstrate for the first time the synergism between midkine and platelet-derived growth factor in cell migration.
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PMID:Haptotactic migration induced by midkine. Involvement of protein-tyrosine phosphatase zeta. Mitogen-activated protein kinase, and phosphatidylinositol 3-kinase. 1134 82

Chondroitin sulfate (CS) is a glycosaminoglycan that composed of hexosamine (D-galactosamine) and hexuronic acid (D-glucuronic acid) unit arranged in an alternating unbranched sequence. CS is an essential component of the extracellular matrix (ECM) of connective tissue. It is mainly covalently attached to core proteins in the form of proteoglycans so that it exhibits specific interactions with proteins for cell growth, differentiation, division and migration. In this study, CSs were purified from the cartilage and backbone of sturgeon (Acipenser sinensis). To characterize their biochemical properties, we performed disaccharide compositional analysis after chondroitinase ABC digestion, high performance size exclusion chromatography (HPSEC) and (1)H-NMR spectroscopy. We also investigated the effects of CSs on fibroblast proliferation and adhesion to determine whether wound healing was accelerated in vitro and proliferation of different mitogen-activated protein kinases (MAPK) signaling pathways was facilitated. The CS purified from sturgeon cartilage was primarily composed of 4-sulfated CS (88.8%) and sturgeon backbone CS contains more than 60% 6-sulfated CS. The average molecular weights of CSs obtained from sturgeon cartilage and backbone were found to be 8 and 43 kDa, respectively. Our results showed that both CSs are able to increase cell adhesion, induce proliferation and migration on fibroblasts and may accelerate wound healing by inducing MAPK signaling pathways.
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PMID:Isolation and characterization of chondroitin sulfates from sturgeon (Acipenser sinensis) and their effects on growth of fibroblasts. 2068 17