Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S49 lymphoma tissue culture cells arrest in the G1 phase of the cell cycle when treated with agents that elevate endogenous cyclic adenosine 3':5'-monophosphate (cAMP), such as cholera toxin or exogenously added active congeners of cAMP such as N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (Bt2cAMP). This phenomenon requires that cells contain the appropriate receptors: Mutant cells deficient in adenylyl cyclase fail to arrest in response to cholera toxin, and another mutant that lacks cAMP-dependent protein kinase does not respond to cholera toxin or to Bt2cAMP. The size distribution of cell populations treated with Bt2cAMP changes in a manner that reflects only the perturbation of cell cycle distribution. Arrested G1 cells in particular have the same volume as the G1 cells of an exponentially growing population. When G1 cells that have been arrested by Bt2cAMP are grown in fresh medium free of Bt2cAMP, they begin to reenter S phase after a delay of about 6 hr and do so with pseudo-first-order kinetics, with a half-life of 5 hr. These and other properties previously described suggest that cAMP regulates S49 cell growth by physiologically significant rather than artifactual mechanisms.
Cancer Res 1978 Nov
PMID:Regulation of S49 lymphoma cell growth by cyclic adenosine 3':5'-monophosphate. 21 91

Because S49 cells are senstivie to killing by cyclic AMP (cAMP), mutants can be selected which have a variety of defects in their ability to generate or respond to cAMP. One class of mutants, that with deficiencies in cAMP-dependent protein kinase, has been extensively characterized genetically and biochemically.
Natl Cancer Inst Monogr 1978 May
PMID:Mouse lymphoma cells with mutations of cyclic AMP-dependent protein kinase. 21 62

When L2C leukaemic B lymphocytes from guinea-pigs were incubated in vitro with antibody directed to their surface immunoglobulin (Ig), a rapid rise in intracellular adenosine 3':5'-phosphate (cyclic adenosine monophosphate, cAMP) was observed. Estimation of cAMP was by a protein-binding assay using bovine adrenal protein kinase. Increases up to 30-fold occurred within 30 seconds of incubation at 37 degrees C, to be succeeded by a fall which reached the basal level between 5 and 7 min. The response was proportional to the amount of antibody present. Cross-linking of surface Ig by the antibody was necessary, bivalent (Fab'gamma)2 from the antibody gave a rise in cAMP similar to that given by the parent molecule, whereas monomeric Fab'gamma was ineffective unless it was subsequently cross-linked by anti-antibody. The rise was too rapid to have required capping of the surface Ig for its induction. Not all perturbations of the plasma membrane by antibody induce such a surge in cAMP, since anti-beta2 microglobulin, also reacting with the lymphocyte surface, failed to alter cAMP concentration. The results emphasize that immunotherapy can be influenced by antibody altering the metabolic activity of target cells, quite apart from activation of immunological cytotoxic pathways.
Br J Cancer 1979 Apr
PMID:Antibody-induced changes in levels of cyclic adenosine monophosphate in leukaemic lymphocytes. 22 Oct

After a single injection of diethylnitrosamine (200 mg/kg), there was a rapid increase in the activity ratio of hepatic cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (within 1 hr) followed by the induction of ornithine decarboxylase which was detectable by 3 hr. Both the cyclic AMP-dependent protein kinase activity ratio and the activity of ornithine decarboxylase were significantly elevated above controls for 7 days following the administration of diethylnitrosamine. A single noncarcinogenic dose of diethylnitrosamine (25 mg/kg) did not increase the cyclic AMP-dependent protein kinase activity ratio or induce ornithine decarboxylase activity at 24 hr postadministration. However, serial administration of diethylnitrosamine (25 mg/kg) for 4 or 7 days resulted in an increased activity ratio of cyclic AMP-dependent protein kinase and increased ornithine decarboxylase activity. This is the first report of a prolonged increase in both the activity ratio of hepatic cyclic AMP-dependent protein kinase and the activity of ornithine decarboxylase in response to a single carcinogenic dose of diethylnitrosamine.
Cancer Res 1979 Aug
PMID:Prolonged induction of hepatic ornithine decarboxylase and its relation to cyclic adenosine 3':5'-monophosphate-dependent protein kinase activation after a single administration of diethylnitrosamine. 22 43

Since the effects of cyclic nucleotides are mediated via protein kinases activation, we have studied the properties and regulation of these enzymes in cytosol and particulate fraction of normal cerebral tissues and of some human brain tumors. We found that distribution and activity of cyclic nucleotide-dependent protein kinases are regulated differently among various brain tumors and in comparison to normal gray and white matter. Pathological tissues show an higher cGMP-dependent protein kinase and this biochemical pattern is particularly evident in tumors with more pronounced malignancy. These data further confirm the hypothesis of a correlation between the increase of cGMP function and cellular growth and malignancy.
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PMID:Basal, cAMP- and cGMP-dependent protein kinases in human brain tumors. 23 64

The nonhistone proteins of Ehrlich ascites tumor chromatin have been separated into a loosely bound and two tightly bound protein fractions by sequential extraction of chromatin with 0.35 M NaCl and 2 M NaCl:5 M urea. The nonhistone proteins thus obtained were examined for their chemical composition and distribution of DNA polymerase, RNA polymerase, and protein kinase activities. In addition, the effect of these nonhistone proteins on transcription of DNA in vitro has been determined. The results indicate that these nonhistone proteins, fractionated on the basis of their extractability, exhibit varied compositional characteristics and play different functional roles in the synthesis of DNA and RNA and in the possible control of gene activity.
Cancer Res 1976 Sep
PMID:A comparison of the loosely bound and tightly bound nonhistone proteins from Ehrlich ascites tumor chromatin. 97 79

DNA-dependent RNA polymerase A (or 1) was purified from murine myeloma MOPC 21 by diethylaminoethyl Sephadex chromatography. Further separation from DNA polymerases, protein kinase and DNA endonuclease was accomplished by polyriboadenylate-Sepharose affinity chromatography followed by gradient centrifugation. Yields following chromatography were 100%, but following gradient centrifugation only 25 to 30% of the activity remained. Addition of low-molecular-weight components increased yields to 50 to 60%. Several species of myeloma polymerase A could be detected, and subunits of 190,000 and 125,000 daltons were identified. No evidence of phosphorylation of the polymerase was found.
Cancer Res 1976 Mar
PMID:Purification, analysis, and subunits of myeloma (MOPC 21) DNA-dependent RNA polymerase A (1) by polyriboadenylate-sepharose. 125 70

The growth of new blood vessels plays an important role in the pathogenesis of several diseases including cancer, diabetes, and arthritis. Beta-cyclodextrin tetradecasulfate, when administered with an appropriate steroid inhibits angiogenesis, and can stimulate angiogenesis when given alone. The regulation of angiogenesis is not well understood, and the mechanism of action of beta-cyclodextrin tetradecasulfate is similarly not well defined. Ecto-protein kinase activity that utilizes extracellular ATP has recently been reported on several types of cells. Human neutrophils appear to possess two distinct ecto-protein kinase activities; one that phosphorylates exogenous substrates including vitronectin and basic fibroblast growth factor, and one that phosphorylates endogenous cell-surface proteins. This report shows that beta-cyclodextrin tetradecasulfate inhibits the phosphorylation of the exogenous substrates casein, vitronectin (the major ecto-protein kinase substrate in serum), and basic fibroblast growth factor by human neutrophil ecto-protein kinase activity. In contrast, beta-cyclodextrin tetradecasulfate had no effect on the phosphorylation of endogenous cell-surface proteins by the neutrophil ecto-protein kinase activity. Ecto-protein kinase activity that was inhibited by beta-cyclodextrin tetradecasulfate was also detected on porcine aortic and human umbilical vein endothelial cells. The effects of beta-cyclodextrin tetradecasulfate on ecto-protein kinase activities may play a role in its effects on angiogenesis.
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PMID:The angiogenesis inhibitor beta-cyclodextrin tetradecasulfate inhibits ecto-protein kinase activity. 128 48

Chemoprevention of colon cancer is emerging as an alternative to therapy with a broad potential for reducing cancer incidence in defined high-risk groups and the general population. Besides several chemopreventive agents in use and under investigation, D,L-alpha-difluoromethylornithine (DFMO) and piroxicam have been shown to effectively inhibit colon carcinogenesis in rodents. A variety of proliferation-related parameters have been suggested as potential intermediate markers of cancer risk that could be used to monitor the progress of chemoprevention in clinical trials. We have investigated the effect of chemopreventive agents, DFMO, and piroxicam on mucosal ornithine decarboxylase (ODC) and tyrosine-specific protein kinase (TPK) activities during different stages of azoxymethane (AOM)-induced colonic carcinogenesis in male F344 rats in order to examine the plausibility of using these enzymes as intermediate biochemical markers of colon cancer. Groups of male F344 rats were fed modified AIN-76A diets containing 0 or 150 ppm piroxicam or 4000 ppm DFMO and given s.c. injections of AOM dissolved in normal saline at a dose of 15 mg/kg body weight/week, once weekly, for 4 weeks. Vehicle control groups received s.c. equal volumes of normal saline. Groups of animals were then sacrificed at 0, 4, 16, 24, and 32 weeks after AOM or saline treatment, and their colonic mucosa was analyzed for ODC and TPK activities. AOM treatment significantly increased mucosal ODC as well as TPK activities. AOM-induced ODC and TPK activities were significantly suppressed by dietary DFMO progressively at all stages of colon carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Cancer Epidemiol Biomarkers Prev
PMID:Effect of chemopreventive agents on intermediate biomarkers during different stages of azoxymethane-induced colon carcinogenesis. 130 73

Cell cycle arrest in G2 phase is a common response to a variety of DNA-damaging agents. The coupling between DNA damage and G2 arrest was studied in synchronized HeLa cells using camptothecin, a highly specific inhibitor of topoisomerase I that damages DNA through the formation of reversible topoisomerase I-DNA cleavable complexes. Brief camptothecin treatment of early S-phase HeLa cells caused arrest at G2 phase and abolished the activation of p34cdc2 protein kinase. Both tyrosine dephosphorylation of p34cdc2 and cyclin B accumulation were altered. These cell cycle-dependent changes were not observed when DNA replication was inhibited by aphidicolin during the brief camptothecin treatment. Our results suggest that to produce G2 arrest, active DNA synthesis is required at the time of camptothecin treatment, as was previously shown for camptothecin-induced cytotoxicity. Furthermore, our results suggest that the interaction of the replication fork with DNA damage may ultimately trigger altered regulation of p34cdc2/cyclin B, leading to cell cycle arrest at the G2 phase.
Cancer Res 1992 Apr 01
PMID:The involvement of active DNA synthesis in camptothecin-induced G2 arrest: altered regulation of p34cdc2/cyclin B. 131


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