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 (MK) is a heparin-binding growth factor that promotes cell migration, cell growth and cell survival. The promotion of migration of inflammatory cells, especially macrophages, by MK is involved in formation of a vascular abnormality, i.e. neointima formation. MK-induced migration of peritoneal exudate macrophages was inhibited by heparin, chondroitin sulfate E and dermatan sulfate, but not by chondroitin sulfate D or chondroitin 6-sulfate. Digestion of macrophages with chondroitinase ABC as well as chondroitinase B decreased the migratory activity. However, heparitinase digestion showed only slight effects. These results indicated that a chondroitin sulfate, i.e. an E-type oversulfated structure with dermatan sulfate domain, is involved in MK-induced migration of macrophages. Although a chondroitin sulfate proteoglycan, receptor-type protein tyrosine phosphatase zeta (PTP zeta), participates in MK-induced migration of neurons and osteoblasts, PTP zeta was not detected in macrophages. The MK-induced migration was inhibited by PP1, wortomanin, PD 98059 and vanadate, indicating that the downstream signaling system, which includes Src, PI3 kinase and ERK as important components, is shared with other MK signaling systems in which PTP zeta is involved.
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PMID:Requirement of chondroitin sulfate/dermatan sulfate recognition in midkine-dependent migration of macrophages. 1192 7

Midkine (MK), a heparin-binding growth factor, suppresses apoptosis of embryonic neurons in culture, induced by serum deprivation. Receptor-type protein tyrosine phosphatase zeta (PTP zeta) is a chondroitin sulfate proteoglycan with a transmembrane domain and intracellular tyrosine phosphatase domains. The activity of MK was abolished by digestion with chondroitinase ABC, or addition of the antibody to PTP zeta, while digestion with heparitinase showed no significant effect. These results suggested that the survival-promoting signal of MK was received by a receptor complex containing PTP zeta. Low density lipoprotein receptor-related protein (LRP) has been identified as another component of the signaling receptor. Ectodomains of two related proteins expressed on neurons, namely LRP6 and apoE receptor 2, were FLAG-tagged and examined for MK binding, using MK-agarose column. Both the ectodomains were found to exhibit calcium-dependent binding to MK. These proteins may participate in MK signaling in certain cases. The survival-promoting activity of MK was abolished by PP1, an inhibitor of src protein kinase, pertussis toxin, an inhibitor of G protein-linked signaling and sodium orthovanadate, an inhibitor of PTPs.
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PMID:Receptor-type protein tyrosine phosphatase zeta as a component of the signaling receptor complex for midkine-dependent survival of embryonic neurons. 1257 68