Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The subcellular distribution of adenylate cyclase, cyclic-AMP phosphodiesterase, protein kinases and phosphoprotein phosphatase in bloodstream forms of Trypanosoma brucei was determined by isopycnic sucrose-gradient centrifugation of post-large-granule extracts. Cyclic-AMP phosphodiesterase was almost entirely soluble whereas adenylate cyclase was membrane-bound. The latter enzyme appeared to be absent from the plasma-membrane fraction but copurified with acid phosphatase and acid phosphodiesterase indicating a possible association with the flagellar pocket. At least two protein kinase activities could be distinguished as based on their distribution profiles in gradients, their preference for exogenously added acceptor protein and their inhibition and stimulation by suramin and nucleoside, respectively. Suramin-sensitive protein kinase co-purified with the plasma-membrane marker alpha-D-glucosidase and a nucleoside-stimulated protein kinase behaved as a typical cell-sap enzyme. Phosphoprotein phosphatase activity was found to be mainly soluble but a small part seemed to be associated with plasma membranes.
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PMID:Subcellular distribution of adenylate cyclase, cyclic-AMP phosphodiesterase, protein kinases and phosphoprotein phosphatase in Trypanosoma brucei. 629 15

Suramin is a prototype of a new class of anticancer drugs. We investigated the action of suramin on the signal transduction pathways to DNA topoisomerase II (Topo II). Suramin showed a growth-inhibitory effect on a human lung cancer cell line (PC-9) with an IC50 of about 160 micrograms/ml. Suramin inhibited the catalytic activity of Topo II with an IC50 of about 100 micrograms/ml without stabilization of the cleavable complex of DNA and Topo II. Suramin decreased the phosphorylation of Topo II with an IC50 of 175 micrograms/ml, but did not change the degree of Topo II expression. These IC50 values for inhibition of catalytic activity and phosphorylation of Topo II were equivalent to the growth-inhibitory dose determined by tetrazolium dye assay. Phosphorylation of the tyrosine residues of Topo II was not changed by suramin. In the presence of okadaic acid, a potent inhibitor of serine/threonine protein phosphatase, suramin also decreased the phosphorylation of Topo II, suggesting that the drug did not act on the serine/threonine protein phosphatases inhibited by okadaic acid. Suramin also inhibited the protein kinase C (PKC) activity of PC-9 cells. These results suggest that suramin decreases the phosphorylation of Topo II mediated by PKC. This effect of suramin might cause the inhibition of Topo II activity resulting in the growth inhibition of tumor cells.
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PMID:Suramin inhibits the phosphorylation and catalytic activity of DNA topoisomerase II in human lung cancer cells. 829 4

Suramin has long been used for the treatment of Gambian and Rhodesian trypanosomiasis and oncocerciasis. More recently, the demonstration that suramin inhibits DNA polymerases, reverse transcriptase and the lymphocyte terminal deoxynucleotidyl transferase has led to its clinical trials for the treatment of AIDS and cancer. The precise nature of suramin's anti-neoplastic action is not clear at this time. Suramin rapidly alters the tyrosine-specific phosphorylation of cellular proteins in many cancer cell lines. Here we demonstrate that suramin strongly inhibits the activity of CD45, the principal tyrosine specific protein phosphatase of T lymphocytes. Suramin-induced inactivation of CD45 is noncompetitive, irreversible and complete within 10 min. The ability of suramin to block CD45 mediated phosphatase function provides both new insight into the mechanism of action of this agent and a useful new probe for studies of T cell activation.
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PMID:Suramin, an experimental chemotherapeutic drug, irreversibly blocks T cell CD45-protein tyrosine phosphatase in vitro. 833 52

We have previously demonstrated that elevation of free cytosolic Ca(2+) concentration at the time of differentiation of chondroblasts was mainly due to a Ca(2+) influx and it was indispensable to cartilage formation in chicken high density mesenchymal cell cultures (HDC) [C. Matta, J. Fodor, Z. Szijgyarto, T. Juhasz, P. Gergely, L. Csernoch, R. Zakany, Cytosolic free Ca(2+) concentration exhibits a characteristic temporal pattern during in vitro cartilage differentiation: a possible regulatory role of calcineurin in Ca-signalling of chondrogenic cells, Cell Calcium 44 (2008) 310-323]. Here, we report that chondrogenic cells secreted ATP and administration of ATP to the culture medium evoked Ca(2+) transients exclusively in the presence of extracellular Ca(2+) and only on day 3 of culturing, when the final commitment of chondroblasts occurs. Moreover, ATP caused elevated protein expression of the chondrogenic transcription factor Sox9 and stimulated cartilage matrix production. Expression pattern of different types of both ionotropic and metabotropic purinergic receptors was detected. Agonists of metabotropic receptors, ADP and UDP did not evoke any Ca(2+) transients and had no influence on cartilage formation, while UTP caused transient elevation of cytosolic Ca(2+) concentration in 3-day-old HDC without stimulating matrix production. Suramin, which blocks all P2X receptors but not P2X(4) did not impede the effects of ATP, furthermore, P2X(4) appeared in the plasma membrane fraction and gave signals with immunocytochemistry only from day 3. In summary, we suggest a role of ionotropic purinergic signalling of P2X(4) in the generation of ATP-dependent Ca(2+) transients of differentiating chondroblasts.
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PMID:Ionotropic purinergic receptor P2X4 is involved in the regulation of chondrogenesis in chicken micromass cell cultures. 1929 18