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:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inhibition of cell replication in two human carcinoma cell lines by various cyclic AMP analogs was explored. In all instances, the addition of the cyclic nucleotide phosphodiesterase inhibitor 1-methyl-3-isoburylxanthine resulted in synergistic growth inhibition by the analogs. A correlation was found between an analog's ability to inhibit growth and its ability to activate protein kinase. A differential effect of the breakdown product 8-bromo-AMP (8-BrAMP) on cell replication in the two cell lines was observed; i.e., one cell type was extremely sensitive to inhibition by 8-BrAMP and the growth inhibition could not be reversed by uridine, whereas the other cell type was less sensitive to 8-BrAMP and the growth inhibition was significantly reversed by uridine.
J Natl Cancer Inst 1979 Oct
PMID:Differential growth inhibition in two human carcinoma cell lines by cyclic adenosine 5'-monophosphate analogs. 9 Jan 51

A clone of neuroblastoma cells has been selected for its ability to survive and multiply at 40 degrees C. This temperature-resistant clone, like clones of neuroblastoma cells selected for resistance to dibutyryladenosine 3':5'-monophosphate (Bt2-Ado-3':5'-P) showed an increased tumorogenicity in animals and an increased saturation density at 37 degrees C. The Ado-3':5'-P-binding proteins and Ado-3':5'-P-dependent protein kinases from the temperature-resistant and non-resistant cells have been partially purified by chromatography on a DEAE-cellulose column. The Ado-3':5'-P-binding proteins from temperature-resistant cells were more sensitive to temperature than the binding proteins from non-resistant cells. After incubation of binding proteins from resistant cells at 37 degrees C, the specific activity of Ado-3':5'-P-binding to proteins was decreased about 50% and the apparent association constant (Ka) for Ado-3':5-p-binding was decreased from 7.4 X 10(7)M-1 to 4.4 x 10(7)M-1. There was no such decrease with binding proteins from non-resistant cells. A decrease in the activity of binding proteins from the temperature-resistant cells, but not of those from non-resistant cells, was also found when the proteins were stored at 2 degrees C. Treatment with 2-mercaptoethanol made binding proteins from the resistant cells less temperature-sensitive. In the absence of added Ado-3:5-P the protein kinase activity from the temperature-resistant cells was about 50% of the activity from non-resistant cells. Kinase activity was increased by addition of Ado-3:5-P and there was a greater increase with kinases from resistant cells. The maximum protein kinase activity was found in the presence of 10muM Ado-3':5'-P for the temperature-resistant cells and 0.1 muM Ado-3':5'-P for the non-resistant cells. The results indicate that the temperature sensitivity of Ado-3':5'-P-binding proteins, and the activity of protein kinase from cells selected for resistance to high temperature, are similar to those of cells selected for resistance to Bt2-Ado-3':5'-P. It is suggested that the temperature sensitivity of Ado-3':5'-P-binding proteins and the activity of Ado-3':5'-P-dependent protein kinases are involved in the regulation of malignancy and of cell growth at different temperatures.
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PMID:Temperature sensitivity of cyclic-adenosine-3':5'-monophosphate-binding proteins, activity of protein kinases and the regulation of cell growth. 17 35

The three major nuclear DNA-dependent RNA polymerases (enzymes I, II and III) were present in nuclear extracts from transplantable R-35 rat mammary tumors. Except for somewhat less enzyme III, their relative distribution resembled that of nuclear extracts from late-pregnant rats. When enzyme II from normal tissue extracts was incubated for RNA synthesis with cyclic AMP, inhibition was frequently observed, but this occurred less often with nuclear extracts from the R-35 tumor. In some experiments with both normal and tumor tissue, cyclic AMP and cyclic GMP increased the apparent activity of nucleolar enzyme Ib and nucleoplasmic enzyme II, respectively. Nuclear extracts from both normal and tumor tissue contain proteins which bind radioactive cyclic AMP and cyclic GMP. Their patterns of binding were not identical. These results are consistent with the following hypothesis: altered binding by the tumor of cyclic nucleotides to putative nuclear 'r-gulatory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to atative nuclear 'regularory' proteins (e.g. protein kinase subunits, or possibly other high affinity cyclic nucleotide-binding proteins unrelated to protein kinases) contributes to and may be responsible for some of the differences in response to cyclic nucleotides that were observed. It is possible that such defects occur in other tumors, or even represent a fundamental defect in all cancer cells. Several explanations for these results are discussed.
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PMID:Solubilized nuclear DNA-dependent RNA polymerases from normal rat mammary glands and from transplantable R-35 rat mammary tumors. 17 42

Cyclic nucleotide levels, protein phosphotransferase activities, and cyclic nucleotide-binding proteins have been determined and partially characterized in the mouse lymphosarcoma P1798. This system is used as a model to understand the function of these activities in a rapidly proliferating cell. Adenosine 3':5'-monophosphate (cAMP) concentrations are 5-fold higher in the lymphosarcoma cells than in thymocytes. In both the thymocytes and malignant tissue, cAMP concentrations are increased by physiological concentrations of epinephrine and prostaglandin. The guanosine 3':5'-monophosphate (cGMP) level in the lymphosarcoma is 0.1 pmole/10(6) cells and is not modified by acetylcholine, prostaglandin F2alpha, or concanavalin A. Four protein phosphotransferase activities have been identified in the lymphosarcoma. These are the cAMP-dependent protein kinase type I and II isozymes and a "histone kinase" and a "phosvitin kinase"; neither of the latter two is regulated by cyclic nucleotides. Characterization of these enzymes was based on fractionation by DE 52 chromatography, substrate specificity, interaction with the protein inhibitor of cAMP-dependent protein kinases, and sucrose gradient sedimentation rates. Both the cAMP-dependent protein phosphotransferase activity and the phosvitin phosphotransferase activity are 2-to 4-fold elevated in the lymphosarcoma cells in comparison to thymocytes. cAMP binding is associated with both the type I and II isozymes and with a fraction tentatively designated as the regulatory subunit of these enzymes. cGMP also binds to this later fraction and to the partially purified fraction containing the type IcAMP-dependent enzyme. The histone phosphotransferase activity of this fraction is also stimulated by cGMP, but studies of the number of binding sites and of absorption to cAMP and cGMP affinity resins indicated that this fraction contains more than one species of cyclic nucleotide-binding protein.
Cancer Res 1976 Sep
PMID:Protein phosphotransferase activities and cyclic nucleotide action in proliferating lymphocytes. 18 45

In the adrenocortical carcinoma cell, in contrast to normal isolated adrenal cells, 10 to 50 muunits of ACTH do not raise the level of adenosine cyclic 3':5'-monophosphate (cyclic AMP), protein kinase activity, and steroidogenesis. This indicates a lesion in the tumor adenylate cyclase system. Two-tenths to 10 mM cyclic AMP and guanosine cyclic 3':5'-monophosphate (cyclic GMP) which stimulate steroidogenesis in a normal cell, activate protein kinase activity in a concentration-response manner without any detectable rise in steroidogenesis in the adrenocortical carcinoma cell. Cycloheximide and actinomycin D do not inhibit the stimulation of the phosphorylation. These results suggest that the tumor cyclic nucleotide-dependent protein kinase activity is unrelated to steroidogenesis and is also not under the transcriptional or translational control steps. Curiously, muM concentrations of cyclic AMP, in contrast to cyclic GMP, stimulate protein kinase activity. In a normal cell, both cyclic AMP and cyclic GMP, in this concentration range, stimulate protein kinase without an increase in steroidogenesis. It is therefore proposed that, in contrast to the normal cell, there is an additional defect in cyclic GMP-dependent protein kinase.
Cancer Res 1977 Feb
PMID:Metabolic regulation and relationship of endogenous protein kinase activity and steroidogenesis in isolated adrenocortical carcinoma cells of the rat. 18 48

Cyclic adenosine 3'5'-monophosphate (cyclic AMP)-dependent and -independent protein kinases were detected and partially characterized in soluble extracts from mouse epidermis. Cylic AMP-dependent histone kinase activity was separated rom cyclic AMP-independent casein kinase activity by DEAE-Sephadex chromatography. The application of the tumor promoters croton oil or 12-o-tetradecanoyl-phorbol-13-acetate to mouse skin caused a rapid increase in the soluble protein extractable from the epidermis resulting in a decrease in the specific activity of both classes of protein kinase when expressed on a protein basis. No change in the activities of either the cyclic AMP-dependent or -independent enzymes was observed when expressed relative to the DNA content.
Cancer Res 1977 May
PMID:Effect of tumor promoters on the activity of cyclic adenosine 3':5'-monophosphate-dependent and -independent protein kinases from mouse epidermis. 19 48

Previous studies with isolated adrenocortical carcinoma 494 cells from this laboratory have indicated that the lack of cyclic adenosine 3':5'-monophosphate (cyclic AMP) control in steroidogenesis in the tumor may be due to the defective cyclic AMP-dependent protein kinase enzyme system. This paper describes the partial purification of such an enzyme. Purification was achieved by precipitation of the tumor homogenate with 30 and 45% ammonium sulfate, adsorption on 3% calcium phosphate gel, and chromatography on DEAE-cellulose. Four major protein peaks were isolated. Peak 2 showed cyclic AMP-binding activity and was investigated further for its kinetic properties. In contrast to the cyclic AMP-dependent protein kinase enzyme found in the normal adrenal gland, the enzyme specifically bound cyclic AMP but failed to phosphorylate exogenous histone. It is postulated that lack of the cyclic nucleotide-dependent kinase activity of the protein kinase enzyme may be responsible for the loss of cyclic AMP-regulated corticosterone synthesis in adrenocortical carcinoma cell. It is further shown that the tumor cyclic AMP-binding enzyme undergoes endogenous phosphorylation, which indicates that it has kinase activity but it is independent of cyclic AMP.
Cancer Res 1977 Sep
PMID:Partial purification and characterization of the defective cyclic adenosine 3':5'-monophosphate binding protein kinase from adrenocortical carcinoma. 19 24

Multiple protein kinase activities were isolated from nuclei of rat and hepatoma 3924A, and purified 40- to 140-fold, respectively. Hepatic protein kinase-I exhibited high activity with casein as substrate, but was relatively inactive with either liver and hepatoma chromatin or mixed histone. In contrast, hepatoma protein kinase-I showed equivalent activity with casein and liver chromatin. Protein kinase-IIA, -IIB and-IIC from both tissues were more active with liver chromatin in comparison to casein and hepatoma chromatin, and exhibited similar electrophoretic profiles of 32P-chromatin.
Cancer Biochem Biophys 1977
PMID:Multiple nuclear protein kinase activities in rat liver and hepatoma 3924A. 21 Sep 25

A new protein kinase-dependent phosphorylation occurs in the nuclei of hormone-dependent, 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced mammary carcinoma following preincubation of tumor slices with cyclic adenosine 3',5'-monophosphate (cAMP). The presence of 17beta-estradiol in the medium inhibits this effect. Both events have been observed in vivo in the nuclei of DMBA-induced tumors. The phosphorylation pattern of nuclei in hormone-independent mammary tumor, DMBA No. 1, however, is not affected by preincubation with either cAMP or estrogen. These findings suggest that the antagonistic effect of cAMP and estrogen in the growth control of mammary tumors is exerted through a specific action on nuclear protein phosphorylation and that these events correlate with the hormone-dependency of the tumors.
Cancer Lett 1978 Oct
PMID:Antagonistic action between cyclic AMP and estrogen in phosphorylation of mammary tumor nuclear proteins. 21 Sep 29

During the growth arrest of 7,12-dimethylbenz(alpha) anthracene-induced rat mammary carcinomas following ovariectomy or N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (DBcAMP) treatment, a change in the specific estrogen and cAMP binding to tumor proteins is observed. Three days after ovariectomy or DBcAMP treatment of the hosts, cAMP binding increases 5- and 2-fold in the nuclei and cytosol of tumors, respectively, whereas nuclear and cytoplasmic estrogen binding decreases by 70 and 25%, respectively. These changes in cAMP- and estrogen-binding activities are detectable within 1 day after ovariectomy or DBcAMP treatment, and the changes are reversed when resumption of tumor growth is induced by the injection of estradiol valerate or cessation of DBcAMP treatment. When 7,12-dimethylbenz(alpha)anthracene-induced tumors fail to regress after ovariectomy or DBcAMP treatment, the change in estrogen and cAMP binding does not occur. Concomitant with the increase of cAMP-binding activity in regressing tumors are increases in histone kinase activity and the cAMP content of the tumors. These increases in cAMP-binding and protein kinase activities are blocked by cycloheximide. These data suggest an interaction between a steroid hormone and cAMP in the growth control of a hormone-dependent mammary tumor.
Cancer Res 1978 Oct
PMID:Inverse relation between estrogen receptors and cyclic adenosine 3':5'-monophosphate-binding proteins in hormone-dependent mammary tumor regression due to dibutyryl cyclic adenosine 3':5'-monophosphate treatment or ovariectomy. 21 Sep 38


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