Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The naphthodianthrone hypericin produces a potent and irreversible inhibition of the epidermal growth factor (EGF) receptor tyrosine kinase activity. The inhibition was time and temperature dependent but did not depend on EGF activation. The IC50 values obtained were 0.37-8.7 microM with membranes incubated for 30 min at 30 degrees or 10 min at 0 degree, respectively. Kinetic analyses with poly(Glu,Ala,Tyr) 6:3:1 [poly(GAT)] as an exogenous substrate were in agreement with the irreversible nature of the inhibition. Irradiation for 30 min with fluorescent light caused a dramatic photosensitizing effect and resulted in an IC50 value of 44 nM. This effect was due to a type I mechanism, since the exclusion of oxygen did not alter the inhibition curve. The inhibition was inversely proportional to the amounts of membranes used, which probably reflects the non-specific sequestration of hypericin into the lipid bilayer. Ser/Thr protein kinases such as protein kinase A, casein kinase 1 and 2 and the enzyme 5'-nucleotidase, were not inhibited by hypericin not even at high concentrations (> 100 microM).
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PMID:Inhibition of epidermal growth factor receptor tyrosine kinase activity by hypericin. 826 42

We show that Escherichia coli produce a factor that inhibits the activity of tyrosine and serine/threonine protein kinases. The factor is a protein found in the periplasmic compartment and is also secreted into the culture medium. Using a particle concentration fluorescence immunoassay specific for tyrosine kinase activity and inhibition of the tyrosine kinase p56(lck), we purified this factor to apparent homogeneity. Analysis of trypsin-digested fragments by mass spectrometry identified the inhibitor as the bacterial periplasmic protein UDP-sugar hydrolase, an enzyme with potent and nonspecific 5'-nucleotidase activity. Overexpression of the enzyme in bacteria leads to coordinate increases in both 5'-nucleotidase and p56(lck) inhibitory activity, confirming the identity of the inhibitor. The kinase inhibitory activity appears to be due to the formation of adenosine, which we show is inhibitory for p56(lck), cAMP-dependent protein kinase, and casein kinase. Overexpression of UDP-sugar hydrolase leads to an increase in the recovery of enteropathogenic E. coli following infection of HeLa cell monolayers and corresponding alterations in tyrosine-phosphorylated host proteins. These results suggest that UDP-sugar hydrolase may be an important factor affecting host cell function following intracellular bacterial infection.
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PMID:Identification of a bacterial inhibitor of protein kinases. Mechanism and role in host cell invasion. 879 49

Because epidermal growth factor (EGF) is likely to be released in the glomeruli during glomerular injury and mesangial cells possess specific receptors for EGF, we thought it to be of interest to examine whether this growth factor could influence the expression of ectoenzymes in cultured human mesangial cells. EGF stimulated 5'-nucleotidase and aminopeptidase N activities in intact human mesangial cells in a time- (24-72 h) and dose-dependent (0.1-50 ng ml(-1)) manner. Maximum stimulation represented 2.7- and 2-fold basal activities for 5'-nucleotidase and aminopeptidase N, respectively. EGF did not influence cyclic AMP production, and its effect on 5'-nucleotidase was additive to that of forskolin or 8-bromo-cAMP. In contrast, genistein (10 mg x ml(-1)), an inhibitor of tyrosine kinase, prevented EGF-dependent stimulation of aminopeptidase N and 5'-nucleotidase, suggesting that protein phosphorylation was involved in the signaling mechanism. EGF stimulated specifically the latter two enzymes since it had no effect on other ectoenzymes including alkaline phosphodiesterase I and Mg2+-ATPase activities. These results demonstrate that EGF, via the control of 5'-nucleotidase and aminopeptidase N, which are implied in adenosine formation and peptide processing, respectively, could play a role in human cultured mesangial cell contractility and proliferation.
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PMID:Epidermal growth factor upregulates aminopeptidase N and 5'-nucleotidase in human glomerular mesangial cells. 985 17

1. Myocardial tolerance against infarction is substantially increased by exposing myocytes to 3-10 min transient ischaemia. In this phenomenon, termed 'preconditioning', the adenosine receptor is one of the redundant triggers and the best characterized factor in the cardioprotective mechanism. 2. An increase in interstitial adenosine during preconditioning is thought to be derived primarily from hydrolysis of 5'-AMP in the myocyte by cytosolic 5'-nucleotidase, although a contribution of ectosolic 5'-nucleotidase remains controversial. Adenosine production during ischaemia is substantially suppressed in the preconditioned myocardium, probably due to a decrease in ATP utilization. 3. The adenosine receptor needs to be activated not only at the time of preconditioning ischemia, but also during ischaemic insult for the preconditioning to be cardioprotective. However, the extent of cardioprotection afforded by preconditioning is primarily determined by the interstitial adenosine level achieved during preconditioning ischaemia, not by the level during sustained ischaemia. These data suggest that a post-receptor mechanism downstream of the adenosine receptor may be up-regulated after preconditioning. 4. Studies in vitro suggest that the subtypes of adenosine receptor relevant to preconditioning against infarction are A1 and A3, the activation of which appears to provide additive protection. The functional interrelationship between these subtypes in vivo remains unknown. 5. An important step downstream of adenosine receptor activation is protein kinase C (PKC), which facilitates opening of ATP-sensitive potassium (KATP) channels, probably leading to enhancement of myocardial tolerance. However, activation of other protein kinases, such as tyrosine kinase, may also be important in preconditioning, depending on the animal species and preconditioning protocols. The PKC isoform and location of KATP channels (i.e. sarcolemmal vs mitochondrial KATP) that induce anti-infarct tolerance in myocytes remain to be identified.
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PMID:Adenosine and preconditioning revisited. 1006 27

The vascular endothelial growth factor (VEGF) family is a novel regulator of endothelial cell proliferation. We assessed the mRNA expression of VEGF, VEGF type C (VEGF-C) and their receptors together with the microvessel density (VD) and microlymphatic vessel density (LVD) in pursuit of their connection and prognostic value in malignant pleural mesothelioma (MPM). We used four human MPM cell lines, 54 MPM tumours and five normal pleural tissues. Expression levels for receptors and ligands were assessed by semiquantitative reverse transcriptase polymerase chain reaction analysis. Microvessels were highlighted by immunohistochemical staining for factor VIII. The discrimination of lymphatics was performed by enzyme-histochemistry for 5'-nucleotidase after adequate inhibition of non-specific activity. The expression levels of VEGF, VEGF-C and VEGFRs were high in all MPM cell lines. The percentages of tumours with higher expression compared to the mean values of normal pleural tissues were 31.5% (17/54) for VEGF, 66.7% (36/54) for VEGF-C, 20.4% (11/54) for fms-like tyrosine kinase (flt)-1, 42.6% (23/54) for kinase insert domain-containing recepter (KDR) and 59.3% (32/54) for flt-4. Significant positive correlations were found between VEGF-C and flt-4, VEGF and KDR, VEGF and flt-1 in tumour tissues. The association between LVD and VEGF-C expression level was especially strong (P< 0.0001, r= 0.63). There were also significant correlations between LVD and flt-4, and VD and VEGF. No correlation, however, was found between LVD and nodal metastasis. VD was a negative prognostic indicator in this study. The associations between VEGFNEGF-C and vessel density suggest that these factors play an important role in angiogenesis and lymphangiogenesis in this tumour, and assessment of vascularity may be a useful prognostic indicator for MPM patients.
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PMID:VEGF and VEGF type C play an important role in angiogenesis and lymphangiogenesis in human malignant mesothelioma tumours. 1048 12