Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The c-fos proto-oncogene is known to be regulated by a variety of hormones, growth factors, and other conditions that alter cellular metabolism. The regulation of c-fos RNA concentrations is known to occur both by altered RNA half-life and/or changes in the transcription rate of the gene. In most cases thus far investigated, induction of c-fos transcription by growth factors occurs very rapidly and transiently. Results presented in this paper show that ouabain, a specific inhibitor of the Na/K-ATPase increases the transcription of c-fos, as well as c-jun, in a variety of cultured cells. However, in contrast to other agents that induce c-fos and c-jun expression, the increased transcription rate of these genes in the presence of ouabain required several hours and remained elevated for at least 16 h. NIH 3T3 cells that have been transfected with deletions of the human c-fos promoter have enabled us to define at least two elements within the promotor that are regulated by ouabain. These include the serum response element and a region between 123 and 222 base pairs 5' to the start site of transcription. We speculate that regulation of the intracellular ion balance through changes in Na/K pump activity may be a general mechanism by which basal transcriptional activity of c-fos is modulated.
 ...
PMID:A role for the Na/K-ATPase in the control of human c-fos and c-jun transcription. 137 80

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.
 ...
PMID:Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities. 160 23

Ras-GAP (GTPase activating protein) is a regulatory protein that stimulates the intrinsic guanosine triphosphatase (GTPase) activity of the proto-oncogene product p21ras. A domain of the neurofibromatosis gene product (NF1) that has sequence similarity to the catalytic domain of Ras-GAP and to yeast IRA gene products also has a specific stimulatory activity toward p21ras GTPase. Arachidonic acid and phosphatidic acid inactivate GAP, but no agents have been identified that stimulate GAP and thereby switch p21ras off. With the use of recombinant Ha-c-Ras and Ras-GAP, NF1, and GAP catalytic domains, it was found that prostaglandins PGF2 alpha and PGA2 stimulated Ras-GAP and that prostacyclin PGI2 inhibited Ras-GAP. The stimulatory effect of PGF2 alpha was saturable and structure-specific and competed with the inhibitory effect of arachidonic acid. Arachidonic acid also inhibited the catalytic activity of NF1, but prostaglandins were not stimulatory. These results suggest a mechanism for the allosteric control of Ras function through the modulation of arachidonate metabolism.
 ...
PMID:Regulation of Ras-GAP and the neurofibromatosis-1 gene product by eicosanoids. 190 23

The expression of Ha-ras in quiescent NIH3T3 cells carrying a glucocorticoid-inducible human Ha-ras gene (Val-Gly mutation at codon 12) stimulates total 86Rb+ influx. This effect is predominantly due to an elevated 86Rb+ uptake through an ouabain-resistant, furosemide-sensitive system. The ouabain-sensitive Na+/K(+)-ATPase is less affected. The transport which is resistant to both inhibitors is not altered by Ha-ras. Overexpression of the Ha-ras proto-oncogene causes only a marginal increase in total 86Rb+ uptake. The stimulation of the furosemide-sensitive influx by Ha-ras is paralleled by an increase in mean cell volume which can be inhibited by furosemide. A rapid stimulation of the furosemide-sensitive Rb+ influx is also observed after addition of bombesin to growth-arrested cells. Furosemide inhibits the mitogenic response after expression of Ha-ras or addition of bombesin. Both the Ha-ras and the bombesin-induced stimulation of the furosemide-sensitive Rb+ transport can be blocked by protein kinase C depletion or the protein kinase C inhibitor staurosporine. In contrast to bombesin-induced phosphatidylinositol-4,5-bisphosphate hydrolysis which is down-modulated by Ha-ras, the stimulation of the furosemide-sensitive Rb+ influx by bombesin is elevated in Ha-ras-expressing cells. This is in accordance with the increased mitogenic activity of bombesin in Ha-ras-expressing cells.
 ...
PMID:Stimulation of K+ transport systems by Ha-ras. 202 40

The ras proto-oncogene products appear to relay intracellular signals via the Ras guanosine triphosphatase (GTPase) activator protein, GAP. In dog epithelial cells expressing human platelet-derived growth factor (PDGF) receptors, binding of PDGF caused approximately one-tenth of the total GAP molecules to complex with the receptor. Studies with mutant PDGF receptors showed that maximum association required both receptor kinase activity and phosphorylatable tyrosine residues at both the identified sites of receptor autophosphorylation.
 ...
PMID:Binding of GAP to activated PDGF receptors. 215 84

1. The expression of c-raf protooncogene in early stages of chemically induced rat liver tumorigenesis was studied in weanling female and adult male Sprague-Dawley rats. After initiation with diethylnitrosamine, promotion by polychlorinated biphenyls (PCBs) or phenobarbital (PB) was studied in the female. Male rats were promoted with PCBs only. 2. The incidence of enzyme-altered foci was evaluated histochemically by demonstrating a deficiency in adenosine-5'-triphosphatase and the emergence of gamma-glutamyl-transpeptidase. C-raf expression was measured in liver tissue containing preneoplastic foci, and in small (< 3 mm in diameter) and large (> 3 mm in diameter) neoplastic nodules up to 36 weeks. 3. Foci numbers amounted to 60-70 per cm2 liver section with both histochemical markers and both promoters in female rats. In male rats foci numbers were about 20-40 per cm2 liver section with both markers and with PCBs as promoting agents. Foci area developed more rapidly in female rats. 4. Small and large nodules were found in females during the entire observation period with both promoting agents, PCBs being more effective than PB. C-raf expression in nodules was increased up to 10-fold in PCB-treated animals compared with untreated controls. No dependence on the size of the nodules was seen. In male rats nodule incidence was very low and c-raf induction was marginal. 5. In conclusion, c-raf proto-oncogene expression correlated with the incidence of foci and nodules, female rats being more sensitive than males.
 ...
PMID:C-raf expression in early rat liver tumorigenesis after promotion with polychlorinated biphenyls or phenobarbital. 752 61

Yes belongs to the Src family of protein-tyrosine kinases. In order to understand molecular aspects of its signaling, we decided to isolate proteins that bind to the modulatory region of the Yes molecule. By generating anti-idiotypic antibodies against the aminoterminal domain of the Yes protein, we have identified, characterized and cloned a cDNA for a novel protein that binds to the Src homology domain 3 (SH3) of the Yes proto-oncogene product. The protein is of 65 kiloDalton (kDa) molecular mass, it is phosphorylated in vivo on serine and is particularly rich in proline. We named it YAP65 for Yes-Associated Protein of 65 kDa. Within the YAP65 sequence, we identified a motif, PVKQPPPLAP, similar to that found in proteins that bind to the SH3 domain of the Abl kinase. Competition assays with synthetic peptides showed the involvement of the predicted proline-rich sequence in binding between YAP65 and the Yes kinase. The YAP65 protein was also shown to bind to other signaling molecules that contain SH3 domains including Nck, Crk and Src. At lower stoichiometry, YAP65 was also shown to bind to the SH3 domains of Abl and guanosine triphosphatase activating protein (GAP). Further characterization of YAP65 should illuminate Yes signaling pathways and could also identify a novel link between protein-tyrosine and serine kinases.
 ...
PMID:Yes-associated protein (YAP65) is a proline-rich phosphoprotein that binds to the SH3 domain of the Yes proto-oncogene product. 803 99

Unlike the alpha subunits of heterotrimeric guanosine triphosphate (GTP)-binding proteins, Ras-related GTP-binding proteins have hitherto been considered not to bind or become activated by tetrafluoroaluminate (AIF4-). However, the product of the proto-oncogene ras in its guanosine diphosphate (GDP)-bound form interacted with AIF4 - in the presence of stoichiometric amounts of either of the guanosine triphosphatase (GTPase)-activating proteins (GAPs) p120GAP and neurofibromin. Neither oncogenic Ras nor a GAP mutant without catalytic activity produced such a complex. Together with the finding that the Ras-binding domain of the protein kinase c-Raf, whose binding site on Ras overlaps that of the GAPs, did not induce formation of such a complex, this result suggests that GAP and neurofibromin stabilize the transition state of the GTPase reaction of Ras.
 ...
PMID:Formation of a transition-state analog of the Ras GTPase reaction by Ras-GDP, tetrafluoroaluminate, and GTPase-activating proteins. 865 79

Human monocytic leukemia THP-1 cells were induced to differentiate into macrophage-like cells by treatment with cardiotonic steroid bufalin, which was previously shown to interact with the Na+, K+-ATPase with similar kinetics to ouabain, a specific inhibitor of the enzyme. This induction of differentiation was characterized by loss of proliferation, cell adherence, increased ability to reduce Nitro Blue tetrazolium (NBT), and increased expression of interleukin 1 beta (IL-1 beta). During this process, bufalin downregulated c-myb and c-myc expressions and induced c-fos and Egr-1 transcripts. Ouabain also caused similar changes in proto- oncogene expression and induced phenotypic markers of differentiated cells at concentrations comparable to bufalin. The 12-O-tetradecanoyl phorbol-13-acetate resistant THP-1 cell variant, which was unresponsive to this agent as to growth inhibition and proto-oncogene expression, responded to bufalin. The finding that protein kinase inhibitor H7 failed to bufalin-mediated c-fos induction further supports the theory that the signal transduction machinery caused by bufalin is separable from the phorbol ester. The cytotoxic effect of high doses of bufalin apparently disappeared in the medium where Na+ was replaced with choline ions. Furthermore, bufalin failed to induce c-fos expression and to downregulate c-myb transcripts in the low-Na+ medium. These findings indicate that an increased intracellular Na+ concentration resulting from the Na+, K(+)-ATPase inhibition possibly triggers the change in proto-oncogene expression evoked by bufalin.
 ...
PMID:A cardiotonic steroid bufalin-induced differentiation of THP-1 cells. Involvement of Na+, K(+)-ATPase inhibition in the early changes in proto-oncogene expression. 869 57

A review of the meeting "The Ras Superfamily of Small GTP-Binding Proteins," FASEB Summer Research Conference, Snowmass, Colorado, 15 through 20 July 2000 The molecular cloning of the human proto-oncogene encoding Ras was reported nearly 20 years ago. Since then, Ras has become the prototypical member of a superfamily of small guanosine triphosphatase proteins. Despite the maturity of this field of research, the discovery of new functions and interactions between the superfamily members continues unabated. Symons and Takai have written a meeting report on the latest findings on the Ras superfamily.
 ...
PMID:Ras GTPases: singing in tune. 1175 38


1 2 3 Next >>