Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological activity of Ras proteins is thought to be controlled by the guanine nucleotide exchange factor and the guanosine triphosphatase activating protein (GAP). Treatment of rat pheochromocytoma PC-12 cells with nerve growth factor (NGF) increased the amount of active Ras guanosine triphosphate complex and stimulated the activities of both the guanine nucleotide exchange factor and GAP. In PC-12 cells that overexpressed the tyrosine kinase encoded by the trk proto-oncogene (a component of the high-affinity NGF receptor), the NGF-induced activation of the regulatory proteins was potentiated. These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins.
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PMID:Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities. 160 23

Colony stimulating factor-1 (CSF-1) stimulates DNA synthesis in quiescent murine bone marrow-derived macrophages (BMM). CSF-1 action has been shown to involve activation of the CSF-1 receptor kinase. The protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (PMA), is itself weakly mitogenic and synergises with CSF-1 for stimulation of BMM DNA synthesis suggesting a possible role for protein kinase C in the stimulation of BMM DNA synthesis. In this report we show that several agents which raise intracellular cAMP (8-bromoadenosine 3':5'-cyclic monophosphate, 3-isobutyl-1-methylxanthine, cholera toxin, and prostaglandin E2) reversibly inhibit DNA synthesis in BMM induced by CSF-1, granulocyte macrophage-colony stimulating factor, interleukin-3, and PMA. The suppressive action of cAMP elevation on the proliferative response to CSF-1 can be manifested even late in the G1 phase of the cell cycle. Several CSF-1-stimulated earlier responses, viz. protein synthesis, Na+/H+ exchange, Na+,K(+)-ATPase and c-myc-mRNA expression, were not inhibited thus showing a striking difference from some other cellular systems involving growth factor-mediated responses. c-fos-mRNA levels were raised and stabilized by the cAMP-elevating agents, and this modulation was not altered by CSF-1. Thus, the signaling pathways in the macrophages involving tyrosine kinase and protein kinase C activation are associated with increased proliferation while those involving elevation of cAMP (and presumably activation of cAMP-dependent protein kinases) appear to have an inhibitory effect.
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PMID:Inhibition of the signaling pathways for macrophage proliferation by cyclic AMP. Lack of effect on early responses to colony stimulating factor-1. 168 93

Vanadate stimulated the release of rat hepatic lipase activity from liver slices into an incubation medium in a time- and dose-dependent manner. Insulin, however, failed to have this stimulatory action, and the release by heparin was recognized, but was not additive to that by vanadate. Amiloride, an inhibitor of tyrosine kinase in some receptors and of the Na+/H+ exchange system suppressed the vanadate-stimulated release. Biochanin A, a different type of tyrosine kinase inhibitor than amiloride, also suppressed the effect of vanadate. The stimulation by vanadate was clearly preserved in Na(+)-, K(+)-, or Ca(2+)-free medium, suggesting that neither the Na+/H+ exchange system, Na+, K(+)-adenosine triphosphatase, nor Ca(2+)-influx into cells is involved in the action of this substance. These results suggest that vanadate-stimulated release of the enzyme activity is associated with the activation of the tyrosine kinase activity.
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PMID:Vanadate-stimulated release of hepatic lipase activity from liver. 181 20

Insulin sensitivity and liver insulin receptor structure were studied in 5-wk-old ducks from two genera (Muscovy and Pekin). In the fasting state, both duck types were equally resistant to exogenous insulin compared with chicken. Despite the low potency of duck insulin, the number of insulin receptors was lower in Muscovy duck and similar in Pekin duck and chicken liver membranes. After 125I-insulin cross-linking, the size of the alpha-subunit of the receptors from the three species was 135,000. Wheat germ agglutinin-purified receptors from the three species were contaminated by an active and unusual adenosinetriphosphatase (ATPase) contaminant (highest activity in Muscovy duck). Sequential purification of solubilized receptor from both duck types on lentil and then wheat germ agglutinin lectins led to a fraction of receptors very poor in ATPase activity that exhibited a beta-subunit size (95,000) and tyrosine kinase activity similar to those of ATPase-free chicken insulin receptors. Therefore the ducks from the two genera exhibit an alpha-beta-structure for liver insulin receptors and a clear difference in the number of liver insulin receptors. Their sensitivity to insulin is, however, similarly decreased compared with chicken.
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PMID:Insulin sensitivity and liver insulin receptor structure in ducks from two genera. 192 34

The regulatory effect of insulin on plasma membrane (Ca2+ + Mg2+)ATPase activity in target tissues for insulin was proposed to be of importance in mediating the hormone's cellular action. Consequently, polyclonal insulin receptor antibodies from patients with type B insulin resistance (B7 and B10) were used as probes to further explore a possible role for this ATPase in insulin action. The antibodies B7 and B10 obtained during the active phase of the disease manifested insulinomimetic actions in rat renal cortical basolateral membranes by displacing [125I]insulin bound to the membranes and stimulating the tyrosine kinase activity of solubilized insulin receptors in a dose-dependent manner. In contrast, these antibodies had insulin antagonistic effects on the membrane (Ca2+ + Mg2+)ATPase activity. While insulin stimulated, both antibodies inhibited the ATPase basal activity in a dose-dependent manner. Furthermore, the stimulatory effect of insulin on the ATPase was completely abolished by the antibodies. Immunoglobulin fractions obtained from patient B10 in the clinically inactive phase of the disease and from pooled normal human sera did not affect basal or insulin-stimulated ATPase activity. The effects of insulin receptor antibodies on basal and insulin-stimulated (Ca2+ + Mg2+)ATPase activities were specific. The receptor antibody did not affect PTH-stimulated (Ca2+ + Mg2+) ATPase activity, nor did it affect other kidney basolateral membrane ATPase basal activities. The data reveal that insulin receptor antibodies have a direct regulatory effect on the plasma membrane (Ca2+ + Mg2+) ATPase. We suggest that the insulin antagonistic effects of the insulin receptor antibodies on the ATPase might explain in part the impaired insulin action in type B insulin resistance.
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PMID:Insulin antagonistic effects of insulin receptor antibodies on plasma membrane (Ca2+ + Mg2+) ATPase activity: a possible etiology of type B insulin resistance. 213 26

A mercurial-insensitive ectoATPase, which was more active with CaATP than with MgATP, was induced when human hepatoma (Li-7A) cells were cultured in the presence of epidermal growth factor (EGF) and cholera toxin. Cholera toxin could be replaced by forskolin, 8-Br-cAMP, butyryl-cAMP, and dibutyryl-cAMP. Requirement for EGF was specific, but EGF was ineffective if added more than 24 h after the addition of forskolin or cholera toxin. It was concluded that induction of the ectoCa2(+)-ATPase was a consequence of the synergistic actions of EGF and cyclic AMP. The tyrosine kinase activity of the EGF receptor was essential for the induction of ectoCa2(+)-ATPase, since enzyme induction was abolished by a tyrosine kinase inhibitor, genistein. Cycloheximide and actinomycin D were also inhibitory to enzyme induction, indicating that enhancement of enzyme activity by EGF and cAMP was not due to post-translational modification. The results of this and previous investigations established that the two ectoATPases of Li-7A cells are under different regulation.
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PMID:Synergistic modulation of ectoCa2(+)-ATPase activity of hepatoma (Li-7A) cells by epidermal growth factor and cyclic AMP. 217 88

The inhibitory effects of Ca2+-binding proteins on tyrosine phosphorylation of p36 protein isolated from bovine intestinal epithelium by immunoprecipitated p130fps were investigated. S-100 protein dose dependently inhibited the p36 phosphorylation, and calmodulin weakly depressed the phosphorylation, whereas parvalbumin and troponin C had no significant effects. The S-100 preparation purified from bovine brain did not contain phosphatase activity or ATPase activity. The concentration of ATP did not affect the S-100-mediated inhibition of phosphorylation but the substrate protein, p36, reversed the inhibition. S-100 similarly inhibited the tyrosine phosphorylation of p36 by p60src but did not affect the p36 phosphorylation by protein kinase C. S-100 inhibited the tyrosine kinase activity of p130fps using the other substrates tested as well. These results suggest that S-100 interacts with the substrate binding site of retroviral tyrosine-specific protein kinases and may play a regulatory role in the tyrosine phosphorylation.
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PMID:Modulation of tyrosine phosphorylation of p36 and other substrates by the S-100 protein. 283 78

Insulin receptor with high insulin binding and tyrosine kinase activities has been prepared from human placenta. Based on a molecular mass of 306 kDa for the receptor (the value obtained from the sum of the amino acid residues), this preparation is capable of binding 1.48 mol of insulin per mol of receptor. The receptor is free from phosphatase and ATPase activity and is not stimulated by sodium vanadate. Autophosphorylation is linear with respect to receptor concentration, and the 32P incorporated is stable even in the presence of a 100-fold excess of unlabeled ATP. The Km for ATP is 208 microM. N-Ethylmaleimide inhibits autophosphorylation. Alkylation with 3H-labeled N-ethylmaleimide results in the incorporation of 1.13 +/- 0.37 mol of N-ethylmaleimide per mol of insulin binding activity exclusively into the beta subunit of the receptor. The nonhydrolyzable ATP analog adenosine 5'-[beta,gamma-imido]triphosphate stimulates autophosphorylation of the receptor, an effect that is evident at ATP concentrations below 1 mM. The stimulatory effect of adenosine 5'-[beta,gamma-imido]triphosphate is the result of increasing the binding of insulin to the alpha subunit, and this reflects itself in a shift to the left of the insulin dose-response curve for autophosphorylation. The same is true for ATP. As a consequence, it is now possible to reconcile the concentration of insulin necessary for stimulating the autophosphorylation reaction with physiological levels and with the levels of insulin required for its classical biological effects.
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PMID:ATP sensitizes the insulin receptor to insulin. 284 8

Insulin receptors from chicken liver and brain were studied following alterations in the nutritional state. Chickens were either fasted for 48 h, fasted for 48 h and then refed for 24 h, or fed a regular diet ad libitum. 125I-Porcine insulin binding was significantly elevated in liver membranes from the fasted animals and lowered in refed chickens when compared to preparations from ad libitum fed chickens. These changes in 125I-insulin binding were inversely related to the levels of plasma insulin and since receptor affinities for insulin were similar in each group, they probably represent alterations in receptor number. Apparent Mr of alpha subunits of the insulin receptors was unaffected by alterations in the nutritional states. The presence of ATPase-like activities that co-eluted with liver insulin receptors from wheat germ agglutinin lectin columns but not from pea lectin columns necessitated the use of both pea and wheat germ agglutinin for liver insulin receptor purification. The insulin receptors purified from both lectin columns were recognized by anti-insulin receptor antiserum and had similar affinities for insulin which were unaltered by the nutritional state. Insulin-stimulatable autophosphorylation of the beta subunit of the insulin receptor was lower in livers from fasted chickens and intermediate in refed chickens. Furthermore, basal and insulin-induced phosphorylation of the artificial substrate poly(Glu,Tyr) 4:1 was significantly less in the fasting state and intermediate in the refed state compared to the ad libitum fed state. Insulin sensitivity (measured as the dose of insulin required for 50% maximal stimulation of kinase activity) was similar in all three states suggesting that the differences in insulin-induced phosphorylation are due to a change in maximal stimulation and not a change in insulin sensitivity. In contrast to the alterations seen with liver receptors, brain insulin receptors were unaffected by these alterations in nutritional state. These findings suggest that: liver insulin receptors are affected by altering the nutritional state; insulin binding to liver membranes is inversely related to plasma insulin levels; and tyrosine kinase is decreased both in fasted and refed animals suggesting an uncoupling of the normal interaction between alpha subunit and beta subunit in liver insulin receptors.
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PMID:Fasting and refeeding alter the insulin receptor tyrosine kinase in chicken liver but fail to affect brain insulin receptors. 353 32

Cytogeneticists recognize that karyotypic abnormalities are associated with specific malignancies. In 1960, Nowell described the Philadelphia chromosome (Ph) and its relationship to chronic myelogenous leukemia (CML). Subsequent work in molecular genetics and biology has revealed that the Ph is a translocation that causes fusion of gene sites that code for the break cluster region (BCR) and the avian blastic leukemia (ABL) proteins. This so-called fusion protein is present in a large percentage of the patients who have CML. A related fusion protein is seen in about one third of patients with acute lymphoblastic leukemia. The BCR-ABL fusion protein results in increased tyrosine kinase activity. The mechanism of action is thought to be via signal transduction related to guanosine triphosphatase activating protein which interacts with a ras-p21 binding protein. Acute promyelocytic leukemia (APL) is associated with the cytogenetic abnormality of t(15;17). This alters the promyelocytic leukemia (PML) and the retinoic acid receptor alpha (RARA) gene sites. Two fusion proteins are the result of this cytogenetic abnormality. They are termed PML-RARA and RARA-PML. Only one, the PML-RARA, is associated with APL. The PML-RARA chimeric protein has two zinc finger-like regions. It retains the ligand binding domain of RARA. The protein called PML has some similarities with a family of proteins which are thought to fuse to proto-oncogenes and to act as transforming proteins. The role of classical cytogenetics and the added capability of molecular biology has helped to elucidate some of the potential mechanisms for the development of cancer and provided additional understanding of neoplasia. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytogenetics, gene fusions, and cancer. 748 13


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