Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.6.12 (chondroitinase)
 2,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that an acidic variant (B1) of lysosomal arylsulfatase B from transplanted human lung cancer is phosphorylated on its protein and carbohydrate moieties (Gasa, S., and Makita, A. (1983) J. Biol. Chem. 258, 5034-5039). The present study identifies that a cAMP-dependent protein kinase is responsible for phosphorylation of arylsulfatase B. The protein kinase activity toward the sulfatase was considerably higher in the transplanted lung cancer than in normal lung in the presence of cAMP. B enzyme purified from normal human liver was found to contain 0.6 mol/mol B enzyme, and protein kinase treatment added further 1.3 mol of Pi to give a single phosphopeptide (X). On the other hand, B1 enzyme purified from the transplanted human lung cancer which had been labeled in vivo with 32Pi revealed at least two phosphopeptides (X and Y). Assuming that the sulfatase from normal liver and lung cancer possesses the same number of available phosphorylation sites, phosphorylation of site X which was available only by deliberate phosphorylation of the native, ordinary B enzyme appears to be cancer-associated. Increasing phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease of the activity upon overphosphorylation, using an artificial substrate.
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PMID:Phosphorylation of human lysosomal arylsulfatase B by cAMP-dependent protein kinase. Different sites of phosphorylation between normal and cancer tissues. 243 76

Since a lysosomal arylsulfatase B has been shown to be phosphorylated by a cAMP-dependent protein kinase (cAMP-PK) in transplantable human lung tumor, protein kinase isozymes were investigated in the tumor. Although the kinase of normal human lung comprised both type I and II isozymes at lower level, the tumor kinase was elevated in the activity and occupied almost exclusively by the type II which was responsible for the phosphorylation of arylsulfatase B. The isozyme deviation was also observed in the casein kinase of the tumor with predominance of type II in the tumor in contrast to the coexistence of both types I and II in normal lung.
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PMID:Alterations of protein kinase isozymes in transplantable human lung cancer with special reference to the phosphorylation of arylsulfatase B. 282 63

Previous studies from this laboratory have demonstrated that arylsulfatase B (ASB) is phosphorylated by a protein kinase, which is the first finding of phosphorylation in lysosomal hydrolases. The present study was undertaken to characterize the sites of phosphorylation in ASB from transplanted human lung cancer and from normal human tissues, and to identify type of tumor protein kinase responsible for the phosphorylation of ASB. When ASB purified from liver and placenta was phosphorylated in vitro by a cAMP-dependent protein kinase, it gave a single tryptic phosphopeptide (X) and phosphothreonine. On the other hand, the tumor ASB which had been phosphorylated in vivo demonstrated two phosphopeptides X and Y. Since the tumor ASB had been shown to be phosphorylated both at threonine and serine residues, phosphorylation at threonine residue of peptide X, which is phosphorylated by a cAMP-dependent protein kinase, will be cancer-associated. Through photoaffinity labeling with a labeled cAMP analogue to detect regulatory subunits of cAMP-dependent protein kinase subtypes, it was found that the cAMP-dependent protein kinase in the transplanted lung tumor was largely type II which can be ascribed to the appearance of highly phosphorylated ASB in the tumor.
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PMID:Protein phosphorylation of human lysosomal arylsulfatase B from normal and cancer tissues. 338 98

An acidic variant form of arylsulfatase B from normal leukocytes and chronic myelogenous leukemia (CML) leukocytes was found to be phosphorylated at its serine and threonine residues through in vivo phosphorylation with 32Pi. However, the predominant phosphorylation site was serine in normal cells, in contrast to threonine in CML cells. A cyclic AMP-dependent protein kinase was responsible for phosphorylation of the sulfatase of CML cells.
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PMID:Protein phosphorylation of lysosomal arylsulfatase B in normal and leukemic leukocytes. 346 94

Many lysosomal hydrolases in cases of human cancer were found to be accompanied by acidic variant forms together with the major hydrolase components. Such variants were found to be phosphorylated not only at their carbohydrate moiety which contributes largely to their acidic property, but also at the protein moiety. We identified a cAMP-dependent protein kinase which is responsible for phosphorylation of arylsulfatase B. The protein kinase activity toward the sulfatase was considerably higher in transplanted lung cancer than in normal lung in the presence of cAMP. The B enzyme purified from normal human liver was found to contain 0.6mol of Pi/mol of B enzyme, and protein kinase treatment added a further 1.3mol Pi to give a single phosphopeptide (X) containing phosphothreonine. On the other hand, the B1 enzyme purified from transplanted human lung cancer which had been labeled in vivo with [32P] Pi revealed at least two phosphopeptides (X and Y). Assuming that the sulfatase from liver and lung cancer possesses the same number of available phosphorylation sites, phosphorylation of site X (Thr) which is available only by deliberate phosphorylation of the native, ordinary B enzyme, appears to be cancer-associated. Increased phosphorylation of the sulfatase resulted in a maximum 50% elevation in arylsulfatase activity, followed by a decrease in the activity upon overphosphorylation, using an artificial substrate.
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PMID:[Phosphorylation of lysosomal hydrolases in human cancer and its significance]. 360 35

Human lung cancer transplanted into athymic mice contains predominantly an acidic variant (designated B1) of lysosomal arylsulfatase B. B1 enzyme was suggested to be phosphorylated and sialylated (Gasa, S., Makita, A., Kameya, T., Kodama, T., Koide, T., Tsumuraya, M., and Komai, T. (1981) Eur. J. Biochem. 116, 497-503). In order to determine the localization of phosphate in B1 enzyme, we labeled in vivo the transplanted tumor with [32P]H3PO4 or [3H]glucosamine and purified B1 enzyme by immunoprecipitation. Bio-Gel chromatography of the labeled B1 enzyme treated with endoglycosidase H demonstrated that both the excluded and included materials were labeled with 32P and 3H. From acid hydrolysate of the excluded materials, phosphorylated serine and threonine were detected. Protein phosphorylation of arylsulfatase was confirmed by in vitro labeling experiments with [gamma-32P]ATP. By incubation of the tumor homogenate with ATP followed by isolation of the enzymes, B1 enzyme had a significant amount of radioactivity, whereas the B enzyme had little; by exogenous protein kinase, partially purified B enzyme was phosphorylated 35 times more than B1 enzyme. Acid hydrolysate of the included materials in the Bio-Gel column demonstrated mannose 6-phosphate and an unknown phosphorylated compound which migrates more than Man-6-P on electrophoresis and chromatography.
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PMID:Phosphorylation on protein and carbohydrate moieties of a lysosomal arylsulfatase B variant in human lung cancer transplanted into athymic mice. 640 42

Purified proteoglycan subunits from human articular, bovine articular and nasal cartilages, and a rat chondrosarcoma were phosphorylated in vitro by beef heart cAMP-dependent protein kinase in the presence of gamma 32P-ATP. In these experiments, a maximum of 1.7 moles of 32P were incorporated per mole of proteoglycan from human cartilage. Phosphorylation was dependent on the presence of cAMP. Analysis by autoradiography revealed that serine residues in the core protein of the proteoglycan were the sites of phosphorylation. Treatment of proteoglycan subunits with chondroitinase ABC and alkaline phosphatase prior to reaction with cAMP-dependent protein kinase increased the incorporation of 32P by 12-30% when compared with untreated proteoglycans. These data indicate that proteoglycans in cartilage can be phosphorylated by cAMP-dependent protein kinase.
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PMID:Phosphorylation of proteoglycans from human articular cartilage by a cAMP-dependent protein kinase. 647 53

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

Laminin-2 promotes basement membrane assembly and peripheral myelinogenesis; however, a receptor-binding motif within laminin-2 and the downstream signaling pathways for motif-mediated cell adhesion have not been fully established. The human laminin-2 alpha2 chain cDNAs cloned from human keratinocytes and fibroblasts correspond to the laminin alpha2 chain variant sequence from the human brain. Individually expressed recombinant large globular (LG) 1 protein promotes cell adhesion and has heparin binding activities. Studies with synthetic peptides delineate the DLTIDDSYWYRI motif (Ln2-P3) within the LG1 as a major site for both heparin and cell binding. Cell adhesion to LG1 and Ln2-P3 is inhibited by treatment of heparitinase I and chondroitinase ABC. Syndecan-1 from PC12 cells binds to LG1 and Ln2-P3 and colocalizes with both molecules. Suppression of syndecan-1 with RNA interference inhibits cell adhesion to LG1 and Ln2-P3. The binding of syndecan-1 with LG1 and Ln2-P3 induces the recruitment of protein kinase Cdelta (PKCdelta) into the membrane and stimulates its tyrosine phosphorylation. A decrease in PKCdelta activity significantly reduces cell adhesion to LG1 and Ln2-P3. Taken together, these results indicate that the Ln2-P3 motif and LG1 domain, containing the motif, within the human laminin-2 alpha2 chain are major ligands for syndecan-1, which mediates cell adhesion through the PKCdelta signaling pathway.
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PMID:A biologically active sequence of the laminin alpha2 large globular 1 domain promotes cell adhesion through syndecan-1 by inducing phosphorylation and membrane localization of protein kinase Cdelta. 1976 14