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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of 3T3-L1 cells with 0.1-1.0 nM insulin results in rapid (5-15 min) activation of a soluble protein kinase that phosphorylates serine residues in ribosomal protein S6. The insulin-stimulated kinase activity is detectable in confluent, nongrowing preadipocytes and adipocytes. In the presence of 2 micrograms of cycloheximide per ml, preconfluent 3T3-L1 cells also respond to insulin by acquiring an S6 kinase activity whose properties are the same as those of the enzyme activity elicited by insulin alone in growth-inhibited cells. The principal insulin-stimulated S6 kinase has a Mr of approximately equal to 50,000-60,000; there is a variable amount of activity that sediments with a Mr of about 80,000. The soluble enzyme exhibits optimal activity between pH 8 and pH 9, requires Mg2+ (10-20 mM), and is inhibited by Ca2+ (0.5 mM), Mn2+ (0.05 mM), and NaF (30 mM). GTP cannot substitute for ATP in the phosphotransferase reaction; cAMP, cGMP, phosphatidylserine plus diolein, the cAMP-dependent protein kinase inhibitor, and heparin (0.7 micrograms/ml) are without effect. Although treatment of 3T3-L1 cells with insulin does not influence the activity or the subcellular distribution of the phospholipid and Ca2+-dependent protein kinase C, exposure to the phorbol tumor promoter phorbol 12-myristate 13-acetate (PMA) results in translocation of protein kinase C to the membrane and activation of a soluble phospholipid and Ca2+-independent S6 protein kinase that has the same magnitude of activity and sedimentation behavior as the insulin-induced activity. Trypsin treatment of either 3T3-L1 cytosolic extracts or partially purified 3T3-L1 protein kinase C generates a small amount of S6 kinase activity of Mr 50,000. This activity, resolved by sucrose gradient centrifugation, is less active than that elicited by either insulin or PMA and, unlike the activities generated by insulin and PMA, is associated with histone kinase activity. The data suggest that the S6 kinase elicited by either insulin or PMA is neither protein kinase C, its phospholipid, and Ca2+-independent proteolytic derivative nor the result of proteolytic activation of an inactive proenzyme that can be reproduced by trypsin treatment of cell extracts in vitro.
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PMID:Activation of S6 kinase activity in 3T3-L1 cells by insulin and phorbol ester. 389 33

Protein kinase capable of phosphorylating 40S ribosomal protein S6 on serine residues has been detected in chicken embryo fibroblasts. This activity appears to be regulated in direct response to expression of pp60v-src in chicken embryo fibroblasts infected with a temperature-sensitive transformation mutant of Rous sarcoma virus. Partially purified S6 kinase was highly specific for S6 in 40S ribosomal subunits. The S6 kinase was not inhibited by calcium or by the heat-stable inhibitor of cAMP-dependent protein kinase, nor was it activated by phosphatidylserine, diacylglycerol, and calcium. Thus, it is distinct from protein kinase C and cAMP-dependent protein kinase, which are capable of phosphorylating S6 in vitro. The tumor-promoter phorbol 12-myristate 13-acetate also stimulated ribosomal protein S6 kinase activity in serum-starved chicken embryo fibroblasts, whereas phorbol, the inactive analog of phorbol 12-myristate 13-acetate, had no effect. S6 kinase activity stimulated by expression of pp60v-src, by phorbol 12-myristate 13-acetate, or by serum growth factors exhibited similar chromatographic properties upon ion-exchange chromatography. These results suggest that a common protein kinase may be activated by three diverse stimuli all involved in regulating cell proliferation.
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PMID:Regulation of a ribosomal protein S6 kinase activity by the Rous sarcoma virus transforming protein, serum, or phorbol ester. 393 63

This study deals with the growth effect of gastrin on two xenotransplantable human gastric carcinomas (SC-6-JCK, poorly differentiated adenocarcinoma; and St-15, mucinous adenocarcinoma) and on one colonic carcinoma (Co-3, well-differentiated adenocarcinoma). In SC-6-JCK, the treatment with s.c. injection of pentagastrin at a dose of 10 micrograms/mouse once daily for 25 days promoted the growth of the tumor transplanted in nude mice, but gastrin had no effect at all on St-15 and Co-3. In SC-6-JCK, the weight, size, and labeling index of [3H]thymidine of the tumor were significantly increased in comparison with those of the control (p less than 0.05). In SC-6-JCK, cyclic adenosine 3':5'-monophosphate (cAMP) in the tumor was increased by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse in nude mice, but such an increase was not observed in St-15 and Co-3. Cyclic guanosine 3':5'-monophosphate in SC-6-JCK was slightly increased by gastrin treatment but was not affected in the other tumors. In SC-6-JCK, at 30 min after gastrin treatment when cAMP showed a maximum increase, the activity ratio of cAMP-dependent protein kinase in the tumor was also elevated. In vitro also, gastrin stimulated cAMP production and cAMP-dependent protein kinase activation. The data suggest that some human gastric carcinomas may have receptor for gastrin.
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PMID:Effects of gastrin on tumor growth and cyclic nucleotide metabolism in xenotransplantable human gastric and colonic carcinomas in nude mice. 608 35

We compared the relative amounts and properties of cyclic adenosine 3':5'-monophosphate (cAMP)-binding proteins in surgical specimens of Wilms' tumor and normal kidney. Cytosolic fractions of both tissues contained type I and type II isozymes of cAMP-dependent protein kinase (adenosine triphosphate: protein phosphotransferase, EC 2.7.1.37). Among tumor samples, the mean ratio of type I to type II cAMP-binding activity was 2.76 +/- 0.52 (S.D.) contrasted with 1.36 +/- 0.23 for normal kidney (p less than 0.001). The total soluble cAMP-binding activities in normal and malignant tissues differed only slightly. Photoaffinity labeling of cytosol from either tissue, using cyclic adenosine 3':5'-[8-azido-32P]monophosphate, disclosed three cAMP-binding proteins (Mr 47,000, 51,000, and 55,000) that were identified as regulatory subunits of the holoenzyme. Three lower-molecular-weight proteins with unknown function were considered to be proteolytic products of the larger proteins. The Mr 47,000 protein, a monomeric regulatory subunit of type I kinase, was clearly the dominant protein in tumor specimens, but it was much less abundant in normal kidney. The temperature sensitivities of the cAMP-binding proteins and their dissociation constants for cyclic adenosine 3':5'-[8-azido-32P]monophosphate incorporation did not differ appreciably between tumor and normal tissues. Wilms' tumor appears to have a full complement of regulatory subunits of cAMP-dependent protein kinase that are capable of normal cellular function.
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PMID:Distribution and properties of type I and type II binding proteins in the cyclic adenosine 3':5'-monophosphate-dependent protein kinase system in Wilms' tumor. 609 71

A cAMP-dependent protein kinase occurs in the intermediate lobe of the rat pituitary gland and the ACTH-secreting tumor AtT-20/D16-16 derived from the mouse pituitary gland. Exposure of either tissue to drugs increasing cAMP production and hormone release (forskolin, cholera toxin, or isoproterenol in the case of the intermediate lobe; forskolin or isoproterenol in the case of the AtT-20 cells) increases the cAMP-dependent protein kinase activity of a tissue homogenate in the absence, but not in the presence, of added cAMP. The potencies of these drugs to induce changes in the protein kinase activity ratio (i.e. enzyme activity in the absence of cAMP to enzyme activity in the presence of 3 microM cAMP) are comparable with their potencies as stimulants of hormone secretion. In either tissue, A23187, a calcium ionophore that stimulates hormone release but not cAMP production, does not change the protein kinase activity ratio. In the case of the AtT-20 cells, dexamethasone blocks the release of ACTH simulated by either isoproterenol or forskolin, but does not alter the enhancement of protein kinase activity induced by these drugs. Conversely, dexamethasone does not block the A23187-stimulated release of ACTH. The data suggest that cAMP modulates (but does not trigger) hormone secretion from the rodent pituitary gland by a mechanism involving activation of the cAMP-dependent protein kinase. Several possible sites for this modulatory effect of cAMP are discussed.
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PMID:Adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase activity in rodent pituitary tissue: possible role in cAMP-dependent hormone secretion. 609 42

A mutant cell line (designated Kin-8), isolated from the Y1 mouse adrenocortical tumor cell line on the basis of its resistance to growth-inhibition by 8-bromoadenosine 3', 5'-monophosphate (8BrcAMP), was resistant to the steroidogenic effects of the cyclic nucleotide analog and did not round up in the presence of 8BrcAMP as did responsive Y1 adrenal cells. In Kin-8 cells, the mutation to cyclic nucleotide resistance was associated with a defective type 1 cAMP-dependent protein kinase activity, suggesting an obligatory role for the enzyme in the regulation of these adrenal functions. In this study, the Kin-8 mutant was fused with a rat glioma cell line (C6) in order to analyze the genetic behavior of the protein kinase mutation in somatic cell hybrids. The growth of C6 glial cells was inhibited by 8BrcAMP and its cAMP-dependent protein kinase responded normally to cAMP. In addition, C6 cells had no capacity for steroidogenesis nor did they round up when treated with 8BrcAMP. In Kin-8 X C6 hybrids, the protein kinase mutation seemed to behave recessively. The growth of hybrid cells was inhibited by 8BrcAMP and the protein kinase responded to cAMP over a normal range. Kin-8 X C6 hybrids, when treated with 8BrcAMP, exhibited steroidogenic activities which were greater than the activity measured in either fusion partner and which had lower ED50 values for 8BrcAMP. In addition, Kin-8 X C6 hybrids rounded up in the presence of 8BrcAMP, a morphologic change unlike that seen with either fusion partner. The effects of 8BrcAMP on the steroidogenic activity and morphology of Kin-8 X C6 hybrids was reminiscent of the effects of the cyclic nucleotide on cAMP-responsive, parental Y1 adrenal cells. These results suggest that cell fusion provided a normal cAMP-dependent protein kinase for Kin-8 cells and led to the recovery of a cAMP-responsive adrenal phenotype. type. These results provide additional evidence in support of an obligatory role for cAMP-dependent protein kinase in the regulation of adrenal steroidogenesis, cell division, and cell shape.
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PMID:Recovery of cyclic nucleotide regulation in protein-kinase-defective adrenal cells through somatic cell fusion. 609 98

In Y1 adrenocortical tumor cells, corticotropin (ACTH), cyclic AMP, and 8-bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated ornithine decarboxylase activity (L-ornithine carboxy-lyase, EC 4.1.1.17) and steroidogenesis. The concentrations required for half-maximal activation of ornithine decarboxylase were 60 pM for ACTH and 1 mM for 8BrcAMP; the concentrations required for half-maximal activation of steroidogenesis were 50 pM for ACTH and 0.2 mM for 8BrcAMP. Ornithine decarboxylase activity increased 1.5 hr after the addition of these agents, reached a maximum between 4 and 6 hr, and then declined. Mutant clones with impaired ACTH-responsive adenylate cyclase systems [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]did not respond to ACTH with increased ornithine decarboxylase activity, but they responded normally to added cyclic AMP. These results indicate that adenylate cyclase and cyclic AMP are necessary for the stimulation of ornithine decarboxylase activity by ACTH. In a series of Y1(Kin) mutants with altered cyclic AMP-dependent protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37), the effects of ACTH on ornithine decarboxylase also were attenuated. These findings suggest that cyclic AMP-dependent protein kinase also plays a necessary role in the stimulation of ornithine decarboxylase activity by ACTH. The effects of ACTH on ornithine decarboxylase in the Kin mutants, however, were quantitatively different from the effects on steroidogenesis and did not closely reflect the degree of defect in cyclic AMP-dependent protein kinase activity. These differences suggest that the pathways of ACTH action leading to stimulation of steroidogenesis and ornithine decarboxylase activity diverge subsequent to activation of the protein kinase.
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PMID:Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase. 624 65

The estrogen and cyclic adenosine 3',5'-monophosphate (cAMP)-binding activities changed markedly when 7,12-dimethylbenz[a]anthracene-induced mammary tumors of Sprague-Dawley rats regressed following daily injections of either tamoxifen or pharmacologic doses of 17 beta-estradiol. cAMP binding increased eightfold to tenfold, whereas estrogen binding increased twofold to threefold in regressing tumor nuclei at 5 days after either treatment, which resulted in an inversion of the ratio of estrogen binding to cAMP binding found in growing tumor nuclei. Concomitantly, both binding activities were depleted from the cytosol. In the regressing tumors, the cAMP level increased twofold and nuclear cAMP-dependent protein kinase activity increased threefold to fourfold, with a 70-80% decrease in the cytoplasmic protein kinase activity. The rise in the nuclear protein kinase activity was abolished when cycloheximide was given with tamoxifen or with high doses of 17 beta-estradiol, which suggests that the increased activity is due to new protein synthesis. In the regressing tumor nuclei, the phosphorylation of the regression-associated proteins increased, whereas the phosphorylation of growth-associated proteins decreased. These data suggest that the mammary tumor regression induced by tamoxifen or high doses of estrogen proceed through a series of cAMP-mediated events.
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PMID:Regression of hormone-dependent mammary tumors in Sprague-Dawley rats as a result of tamoxifen or pharmacologic doses of 17 beta-estradiol: cyclic adenosine 3',5'-monophosphate-mediated events. 625 77

The adenosine 3',5'-cyclic monophosphate (cAMP)-dependent and cAMP-independent kinase activities were measured in the 1,2-dimethylhydrazine (DMH) induced rat colon cancer and in untreated colon. Previous studies had shown that intestinal tumors induced by chronic exposure to DMH contained 2-fold less intracellular cAMP. The present findings indicate that reduction in cAMP-dependent protein kinase activities also occur in colon cancer cells. Similar hydrogen ion dependence (pH 6-7) and approximate association constants (Ka approximately 0.1 microM) were observed for the enzymes existing in both normal and tumor tissues, while the cAMP-dependent tumor protein kinase was found to phosphorylate phosvitin and casein to a greater degree. These recent findings are consistent with the concept that the concentrations of cAMP and activities of its associated enzyme system are inversely related to the cell proliferation state.
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PMID:Adenosine 3',5'-cyclic monophosphate dependent and independent protein kinase activities in 1,2-dimethylhydrazine induced rat colon cancer. 628 71

We have constructed plasmids that direct the synthesis of the Rous sarcoma virus transforming gene (src) product (p60src) in Escherichia coli. A 203-base-pair lac promoter-operator DNA encoding the first eight amino acids of beta-galactosidase was ligated to the 5' end of the src gene from the Prague A strain of Rous sarcoma virus (PrA-RSV) which had been cloned in pBR325. Antiserum, from a tumor-bearing rabbit, directed against pp60src was used to screen bacteria containing the recombinant plasmid for a protein of approximately 60,000 daltons, and several colonies producing a protein immunologically related to pp60src were detected. Partial proteolytic cleavage analysis revealed that the src-related protein produced in bacteria is structurally similar to pp60src immunoprecipitated from PrA-RSV-infected chicken cells. Partially purified src protein from E. coli can be phosphorylated in vitro by the catalytic subunit of cAMP-dependent protein kinase. Tryptic phosphopeptide analysis demonstrated that the catalytic subunit phosphorylated a serine-containing tryptic peptide in the bacterial src protein that comigrated with the phosphoserine-containing tryptic peptide of pp60src immunoprecipitated from 32P-labeled PrA-RSV-infected chicken cells.
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PMID:Construction of plasmids for expression of Rous sarcoma virus transforming protein, p60src, in Escherichia coli. 628 67


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