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)

N-6,O-2'-dibutyryl adenosine 3',5'-monophosphate kills cultured mouse lymphosarcoma cells, but not resistant mutants derived by a single-step clonal selection. Resistant clones lack the cyclic AMP binding proteins present in wild type, cyclic AMP sensitive clones. Both endogenous cyclic AMP, accumulated in response to isoproterenol or cholera toxin, and exogenous dibutyryl cyclic AMP induce cyclic AMP phosphodiesterase, slow growth, and eventually kill wild type cells. In the resistant mutants, however, the endogenous and exogenous cyclic nucleotides appear to be completely inactive. These results indicate that an intracellular receptor for cyclic AMP, previously shown to be associated with a cyclic AMP-dependent protein kinase, mediates cyclic AMP's regulation of growth and phosphodiesterase synthesis.
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PMID:Somatic genetic analysis of cyclic AMP action: characterization of unresponsive mutants. 16 37

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.
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PMID:Protein phosphotransferase activities and cyclic nucleotide action in proliferating lymphocytes. 18 45

Ribosomal RNA (rRNA) synthesis in murine P1798 lymphosarcoma cells is reversibly inhibited by glucocorticoids. The effects of dexamethasone upon nucleolin phosphorylation and upon the amount and activity of casein kinase II have been examined. P1798 cells were exposed to 0.1 microM dexamethasone for 36 h. Cells were labeled in vivo with [32P]orthophosphate followed by immunoprecipitation with anti-nucleolin antibody. Nucleolin phosphorylation was reduced by 60% in dexamethasone-treated cells. Nucleoli were isolated and labeled with [gamma-32P]ATP in vitro. Nucleolin protein was reduced to 40% of control in nuclei from dexamethasone-treated cells. Nucleolin phosphorylation was reduced to 20% of control. Nucleolar casein kinase II activity and protein were also reduced (30-55% and 35-50% of control, respectively) by treatment with dexamethasone. Cycloheximide (10 micrograms/ml for 3 h) reduced the amount and activity of casein kinase II, but did not cause a decrease in nucleolin protein. These observations are discussed relative to the hypothesis that glucocorticoids regulate the amount or activity of proteins of short biological half-life that are involved in the regulation of rRNA synthesis.
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PMID:Effect of dexamethasone on nucleolar casein kinase II activity and phosphorylation of nucleolin in lymphosarcoma P1798 cells. 160 42

The phosphorylation of synthetic peptides derived from the NH2-terminal sequence of smooth-muscle myosin was studied with purified protein kinase C. The protein kinase C phosphorylation domain included both serine residues and threonine residues in the sequence SSKRAKAKTTKKR(G), denoted myosin light chain (1-13) (MLC(1-13)). Kinetic analysis of MLC(1-13) and truncated peptides derived from the parent peptide established that removal of the serine residues had little effect on protein kinase C reactivity. MLC(1-13) had a V/K of 2.4 min-1.mg-1, whereas the V/K of MLC(3-13) was 3.0 min-1.mg-1. Removal of Lys-3 resulted in a 50% decrease in V/K which was attributable to a 50% decrease in apparent Vmax.Arg-4 was established as a significant protein kinase C specificity determinant, since the apparent Km increased 7-fold and the Vmax decreased 3-fold when the parent peptide was truncated at that residue. All peptides studied required calcium and lipid effectors for full activity with protein kinase C, indicating that they are Class C substrates as defined by Bazzi and Nelsestuen (Biochemistry 26 (1987) 5002) for protein kinase C. Other protein kinases, including cyclic AMP- and cyclic GMP-dependent protein kinase, S6/H4 kinase, myosin light-chain kinase and calcium/calmodulin-dependent kinase II, had little or no activity with these peptides. In studies on the purification of lymphosarcoma protein kinase C by several chromatographic procedures, the results showed that the myosin light-chain peptides can provide convenient and well-characterized substrates for purification and mechanistic studies of protein kinase C biochemistry.
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PMID:Synthetic peptides derived from the nonmuscle myosin light chains are highly specific substrates for protein kinase C. 317 14

Cultured mouse lymphosarcoma cells are killed on exposure to 0.1 mM N(6),O(2')-dibutyryl-adenosine 3':5'-cyclic monophosphate. A population of cells resistant to the killing effect of dibutyryl cyclic AMP at concentrations as high as 1 mM was selected. The growth characteristics of the resistant cells were similar to those of the sensitive parental line. However, the resistant cells contain less cytoplasmic cyclic AMP-binding proteins and decreased cyclic AMP-stimulated protein kinase activity. It is proposed that transition from sensitivity to resistance to dibutyryl cyclic AMP in lymphoma cells is connected with a modification of the cyclic AMP-binding protein, which appears to be the regulatory subunit of the cyclic AMP-activated protein kinase.
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PMID:Induction of cytolysis of cultured lymphoma cells by adenosine 3':5'-cyclic monophosphate and the isolation of resistant variants. 434 41

The activation of a cyclic AMP-independent protein kinase by an endogenous protease is described. The H4 phosphotransferase (Masaracchia, R. A., Kemp, B., and Walsh, D. A. (1977) J. Biol. Chem. 252, 7109-7117) from lymphosarcoma cells was isolated in a nonactive form. Activation required ATP and Mg2+ and was shown to be time-dependent. Although Mn2+ was capable of substituting for Mg2+ in the protein kinase reaction, no activation was observed when Mn2+ replaced Mg2+. The protein substrate histone H4 inhibited phosphotransferase activation at concentrations greater than 60 microM. The inhibition was complete in the presence of 100 microM H4. Comparable concentrations of bovine serum albumin did not inhibit the activation. The selective dependence on Mg2+ suggested separate activating and phosphotransferase activities. This was confirmed by heat denaturation in which the activation reaction was shown to be more sensitive to heat inactivation than was the phosphotransferase reaction. The activating enzyme was separated from the protein kinase by column chromatofocusing in the pH range 7-4. The pI of the activating enzyme was greater than 7.0. The pI values of the activated and nonactivated phosphotransferase were 4.8 and 5.3, respectively. The apparent molecular weight of the nonactivated phosphotransferase was 68,000; the activated enzyme was eluted from an S-200 Sephadex column with an apparent Mr = 52,000. Despite many similarities to a protease-activated Ca2+/phospholipid-dependent enzyme isolated from lymphocytes (Ogawa, Y., Takai, Y., Kawahara, Y., Kimura, S., and Nishizuka, Y. (1981) J. Immunol. 127, 1369-1374), the H4 phosphotransferase was not activated by Ca2+, phospholipids, or any combination thereof.
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PMID:Activation of a cyclic AMP-independent protein kinase by an endogenous ATP-requiring protease from lymphosarcoma cells. 630 81

The kinetics for activation of the cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase (PKA) and thymidine incorporation into DNA was investigated in epinephrine- and prostaglandin E1 (PGE1)-treated murine P1798 lymphosarcoma cells. A positive correlation between the duration and extent of PKA activation and accumulation of cyclic AMP and inhibition of thymidine incorporation into DNA was observed with both hormones. Epinephrine and PGE1 elevated intracellular cyclic AMP 34- and 14-fold, respectively. All hormone concentrations which increased cyclic AMP accumulation also promoted inhibition of thymidine incorporation into DNA. In addition, dibutyryl cyclic AMP (50 microM) inhibited thymidine incorporation. No difference in the kinetics for activation of PKA was observed when cells were treated with microM epinephrine or PGE1. With both agents, 50% PKA activation was observed when intracellular cyclic AMP concentrations were elevated 6.5-fold, or to 9 pmol/10(6) cells. In the presence of microM epinephrine, the cyclic AMP concentration was approximately 3-fold greater than that required for maximal PKA activation. In this case, the duration of the activation time for PKA was also 3- to 4-fold longer than that observed with 0.1 microM epinephrine. The data are consistent with a mechanism wherein both epinephrine and PGE1 suppress DNA synthesis by a cyclic AMP-mediated cascade of protein phosphorylation. No evidence for independent cyclic AMP or PKA pools which respond independently to either epinephrine or PGE1 could be detected.
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PMID:Kinetics of adenosine 3':5'-monophosphate-dependent protein kinase activation and inhibition of thymidine incorporation into DNA in P1798 lymphosarcoma cells. 630 87

Ribosomes prepared from murine lymphosarcoma cells were phosphorylated by a cyclic AMP-independent protein kinase designated H4P kinase. H4P kinase was isolated as an inactive enzyme which was activated by Mg2+-ATP and an endogenous converting enzyme. In the absence of preactivation by Mg2+-ATP and an endogenous converting enzyme, H4P kinase catalyzed phosphorylation of 80, 60, and 40 S ribosomal subunits at a low rate. After activation, the H4P kinase selectively catalyzed phosphorylation of the S 6 protein in the 40 S ribosomal subunit. Under the assay conditions selected, at least 90% of the [32P]phosphate transferred to the 40 S ribosomal preparation was incorporated into S 6. The apparent Km for 40 S subunits phosphorylated by H4P kinase was 7.2 microM. The calculated Vmax was 50 nmol of Pi transferred per min/mg. Exhaustive phosphorylation of 40 S subunits resulted in incorporation of 3 mol of phosphate/mol of S 6, in contrast to results reported previously which indicated 0.3 mol of phosphate was transferred by a similar enzyme from reticulocyte (Del Grande, R. W., and Traugh, J. A. (1982) Eur. J. Biochem. 123, 421-428). These data are consistent with a potential role for H4P kinase in the insulin-mediated phosphorylation of S 6 at multiple sites.
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PMID:Phosphorylation of ribosomal protein S6 at multiple sites by a cyclic AMP-independent protein kinase from lymphoid cells. 632 11

The calcium/phospholipid-dependent protein kinase (PKC) and the H4 protease-activated protein kinase (H4PK) from lymphosarcoma cells were separated by CM Sephadex chromatography. PKC activity was increased 10-fold in the presence of calcium and phosphatidylserine, but no activation by Mg+2-ATP preincubation or inhibition by NaF was observed. In contrast, H4PK activity was increased 8-fold by preincubation with Mg+2ATP and NaF completely inhibited this enzyme. Activators and inhibitors of PKC did not affect H4PK activity. The substrate specificity of the H4PK and PKC also differed substantially. On the basis of these data it is concluded that PKC and H4PK are not related enzymes.
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PMID:Resolution and characterization of calcium/phospholipid-dependent protein kinase and H4 protease-activated protein kinase activities in lymphoid cells. 660 26

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