Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

On the basis of data gained by autopsy the frequency of thrombotic and thromboembolic complications (TTK) was investigated by correlation analysis in unselected malignant tumour diseases and in malignant tumour diseases with tumour endocarditis (TE). The following things could be detected: 1. No increase of TTK in malignant tumour diseases compared with the total material, 2. A significant increase of TTK in tumours with TE, 3. A significant increase of TTK with an increasing histological tumour differentiation and an increasing inflammatory current reaction of the tumour, and 4. Parallel behaviour of tumours with TTK and those with TE concerning primary tumours. TTK was interpreted as the cause of an abnormally enhanced tendency of blood coagulation on the basis of an immunocomplex disease, because: 1. The coagulation system is being activated by circulating immunocomplexes, 2. Circulating immunocomplexes will increase with tumour parameters, differentiation, and current reaction, and 3. Frequency of TTK and TE will increase with the same parameters.
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PMID:[Statistical studies on thrombotic complications and the incidence of endocarditis neoplastic diseases]. 616 48

A simple method of cryopreservation (TTK) of lymphocytes is presented. The functional properties of TTK-lymphocytes are examined by the lymphocyte toxicity micro test and in the mixed lymphocyte culture (MLC). 51Cr-release technique is performed as a measure for reversible and irreversible cell damages in the course of the Cryopreservation process.
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PMID:[Functional characteristic of TTK-lymphocytes in vitro, cytotoxicity and mixed lymphocyte culture (MLC)]. 616 98

The transfusion protocols of 70 patients with haematological diseases were evaluated and compared. 68 patients of them received frozen erythrocyte concentrates stored at low temperatures (TTK-EK). A total of 1,183 courses of transfusion with 2,744 transfusion units (TE) were examined for erythrocyte substitution. 841 normal erythrocyte concentrates (n. EK), 905 washed erythrocyte concentrates (gew. EK), and 998 frozen erythrocyte concentrates were transfused. With 0.5% the rate of side-effects after frozen erythrocyte concentrates lay significantly lower than after other suspensions. Indications and advantages of TTK-EK are discussed. The application of double units is further recommended.
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PMID:[The use of erythrocyte concentrates, preserved at low temperature, in hematologic patients]. 617 5

Phosphorylation of rabbit skeletal muscle glycogen synthase by a cyclic nucleotide and Ca2+-independent protein kinase, PC0.7, caused the enzyme to be a better substrate for phosphorylation by another cyclic nucleotide and Ca2+-independent protein kinase, FA/GSK-3. In contrast, phosphorylation by the combination of FA/GSK-3 and cyclic AMP-dependent protein kinase led to less phosphorylation than predicted from the individual actions of the protein kinases. These results are explained in part by the existence of cooperative interactions among the phosphorylation sites of glycogen synthase. Phosphorylation by FA/GSK-3 also correlated with a reduction in the electrophoretic mobility, in the presence of sodium dodecyl sulfate, of the glycogen synthase subunit from an apparent molecular weight of 85,000-86,000 to values of 88,000 and ultimately 90,000. The synergistic phosphorylation by PC0.7 and FA/GSK-3 was associated with an increased formation of the species of reduced electrophoretic mobility. The effects on subunit mobility were also reflected in the behavior of a larger phosphorylated CNBr fragment of glycogen synthase, CB-2, which gave apparent molecular weights of 22,000-27,000 depending on its phosphorylation state.
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PMID:Multiple phosphorylation of rabbit skeletal muscle glycogen synthase. Evidence for interactions among phosphorylation sites and the resolution of electrophoretically distinct forms of the subunit. 630 12

We recently reported the partial purification of a cAMP-independent and Ca2+-calmodulin-independent glycogen synthase kinase from porcine renal cortex (Schlender, K. K., Beebe, S. J., and Reimann, E. M. (1981) Cold Spring Harbor Conf. Cell Proliferation, 389-400). Subsequent purification indicated that the enzyme preparation consisted of at least three forms of glycogen synthase kinase which could be resolved by ATP gradient elution from aminoethylphosphate-agarose (AEP-agarose). The predominant form of glycogen synthase kinase, which eluted from AEP-agarose between 2 and 6 mM ATP, was purified approximately 800-fold and is designated GSK-A1. It had a molecular weight of 45,000-50,000 as determined by gel filtration and sucrose density gradient centrifugation. It catalyzed the transfer of 1 mol of 32P/mol of synthase subunit into a low molecular weight (10,000) CNBr peptide which was tentatively identified as Ser-7 (site 2) by high performance liquid chromatography. This phosphorylation decreased the activity ratio (activity in the absence of glucose-6-P divided by activity in the presence of 7.2 mM glucose-6-P) from 0.95 to about 0.55. GSK-A1 appeared to be specific for and had low s0.5 values for both substrates, ATP (13 microM) and glycogen synthase (0.3-0.4 microM). The enzyme could not use GTP as the phosphate donor. GSK-A1 was not affected by the protein kinase inhibitor, cAMP, cGMP, Ca2+-calmodulin, EGTA, or trifluoperazine and had a broad pH optimum (pH 7.0-8.5). A second form, GSK-A2, was eluted from AEP-agarose between 7 and 9 mM ATP. GSK-A2 could transfer a 2nd mol of 32P/mol of synthase subunit and decreased the activity ratio to 0.30. The interrelation among these multiple forms is not clear, but the data suggest that multiple kinases are required to form the highly inactivated glycogen synthase in renal tissues.
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PMID:Purification and characterization of a cAMP- and Ca2+-calmodulin-independent glycogen synthase kinase from porcine renal cortex. 631 98

Purified rabbit liver glycogen synthase was found to be a substrate for six different protein kinases: (i) cyclic AMP-dependent protein kinase, (ii) two Ca2+-stimulated protein kinases, phosphorylase kinase (from muscle) and a calmodulin-dependent glycogen synthase kinase, and (iii) three members of a Ca2+ and cyclic nucleotide independent class, PC0.7, FA/GSK-3, and casein kinase-1. Greatest inactivation accompanied phosphorylation by cyclic AMP-dependent protein kinase (to 0.5-0.7 phosphate/subunit, +/- glucose-6-P activity ratio reduced from approximately 1 to 0.6) or FA/GSK-3 (to approximately 1 phosphate/subunit, activity ratio, 0.46). Phosphorylation by the combination FA/GSK-3 plus PC0.7 was synergistic, and more extensive inactivation was achieved. The phosphorylation reactions just described caused significant reductions in the Vmax of the glycogen synthase with little effect on the S0.5 (substrate concentration corresponding to Vmax/2). Phosphorylase kinase achieved a lesser inactivation, to an activity ratio of 0.75 at 0.6 phosphate/subunit. PC0.7 acting alone, casein kinase-1, and the calmodulin-dependent protein kinase did not cause inactivation of liver glycogen synthase with the conditions used. Analysis of CNBr fragments of phosphorylated glycogen synthase indicated that the phosphate was distributed primarily between two polypeptides, with apparent Mr = 12,300 (CB-I) and 16,000-17,000 (CB-II). PC0.7 and casein kinase-1 displayed a decided specificity for CB-II, and the calmodulin-dependent protein kinase was specific for CB-I. The other protein kinases were able, to some extent, to introduce phosphate into both CB-I and CB-II. Studies using limited proteolysis indicated that CB-II was located at a terminal region of the subunit. CB-I contains a minimum of one phosphorylation site and CB-II at least three sites. Liver glycogen synthase is therefore potentially subject to the same type of multisite regulation as skeletal muscle glycogen synthase although the muscle and liver enzymes display significant differences in both structural and kinetic properties.
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PMID:Phosphorylation of rabbit liver glycogen synthase by multiple protein kinases. 632 70

A protein kinase, able to phosphorylate casein, phosvitin, and glycogen synthase, was purified approximately 9000-fold from rabbit liver, and appeared analogous to an enzyme studied by Itarte and Huang (Itarte, E., and Huang, K.-P. (1979) J. Biol. Chem. 254, 4052-4057). This enzyme, designated here casein kinase-1, was shown to be a distinct glycogen synthase kinase and in particular to be different from the protein kinase GSK-3 (Hemmings, B.A., Yellowlees, D., Kernohan, J.C., and Cohen, P. (1981) Eur. J. Biochem. 119, 443-451). Casein kinase-1 had native molecular weight of 30,000 as judged by gel filtration. The enzyme phosphorylated beta-casein A or B better than kappa-casein or alpha s1-casein, and modified only serine residues in beta-casein B and phosvitin. The apparent Km for ATP was 11 microM, and GTP was ineffective as a phosphoryl donor. The phosphorylation of glycogen synthase by casein kinase-1 was inhibited by glycogen, half-maximally at 2 mg/ml, and by heparin, half-maximally at 0.5-1.0 microgram/ml, but was unaffected by Ca2+ and/or calmodulin, or by cyclic AMP. Phosphorylation of muscle glycogen synthase proceeded to a stoichiometry of at least 6 phosphates/subunit with reduction in the +/- glucose-6-P activity ratio to less than 0.4. Phosphate was introduced into both a COOH-terminal CNBr fragment (CB-2) as well as a NH2-terminal fragment (CB-1). At a phosphorylation stoichiometry of 6 phosphates/subunit, 84% of the phosphate was associated with CB-2 and 6.5% with CB-1. The remainder of the phosphate was introduced into another CNBr fragment of apparent molecular weight 16,500. Phosphorylation by casein kinase-1 correlated with reduced electrophoretic mobilities, as analyzed on polyacrylamide gels in the presence of sodium dodecyl sulfate, of the intact glycogen synthase subunit, as well as the CNBr fragments CB-1 and CB-2.
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PMID:Glycogen synthase kinases. Classification of a rabbit liver casein and glycogen synthase kinase (casein kinase-1) as a distinct enzyme. 632 24

Isolated rat hepatocytes were incubated in a medium containing 0.1 mM [32P]phosphate (0.1 mCi/ml) before exposure to epinephrine, glucagon or vasopressin. 32P-labeled glycogen synthase was purified from extracts of control or hormone-treated cells by the use of specific antibodies raised to rabbit skeletal muscle glycogen synthase. Analysis of the immunoprecipitates by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate indicated that a single 32P-labeled polypeptide, apparent Mr 88000, was removed specifically by the antibodies and corresponded to glycogen synthase. Similar electrophoretic analysis of CNBr fragments prepared from the immunoprecipitate revealed that 32P was distributed between two fragments, of apparent Mr 14000 (CB-1) and 28000 (CB-2). Epinephrine, vasopressin or glucagon increased the 32P content of the glycogen synthase subunit. CB-2 phosphorylation was increased by all three hormones while CB-1 was most affected by epinephrine and vasopressin. These effects correlated with a decrease in glycogen synthase activity. From studies using rat liver glycogen synthase, purified by conventional methods and phosphorylated in vitro by individual protein kinases, it was found that electrophoretically similar CNBr fragments could be obtained. However, neither cyclic-AMP-dependent protein kinase nor three different Ca2+-dependent enzymes (phosphorylase kinase, calmodulin-dependent protein kinase, and protein kinase C) were effective in phosphorylating CB-2. The protein kinases most effective towards CB-2 were the Ca2+ and cyclic-nucleotide-independent enzymes casein kinase II (PC0.7) and FA/GSK-3. The results demonstrate that rat liver glycogen synthase undergoes multiple phosphorylation in whole cells and that stimulation of cells by glycogenolytic hormones can modify the phosphorylation of at least two distinct sites in the enzyme. The specificity of the hormones, however, cannot be explained simply by the direct action of any known protein kinase dependent on cyclic nucleotide or Ca2+. Therefore, either control of other protein kinases, such as FA/GSK-3, is involved or phosphatase activity is regulated, or both.
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PMID:Control of glycogen synthase phosphorylation in isolated rat hepatocytes by epinephrine, vasopressin and glucagon. 643 31

Two cell lines, TTK-1(E) and TTK-1(F), derived from normal human early decidual tissue have been maintained in culture through forty subcultures since July, 1979. These cell lines were transplanted subcutaneously into nude mice at 6 weeks of age to investigate their tumorigenicity. Rapidly growing tumor nodules formed at the site of implantation. The incidence of tumor growth was 60% in TTK-1(E) and 80% in TTK-1(F). The tumor tissues were composed of poorly differentiated cells arranged in cord-like and/or gland-like structures, and showed the malignant histological characteristics. Light microscopic and electron microscopic studies revealed that the properties of the tumor cell populations are identical with those of the culture cells of the two cell lines before implantation. These results obviously indicated that the tumors had grown from the implanted cells. Although the tumors developed from the respective two cell line showed some common histological features, they apparently differed in light microscopic and electron microscopic findings. Tumorigenesis with malignant features could be attributed to the in vitro spontaneous neoplastic transformations during successive subcultures, which might be useful as an in vitro model of endometrial carcinogenesis.
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PMID:[Tumorigenicity of the cell lines (TTK-1 cell lines) derived from normal human decidua in nude mice]. 651 29

Rat livers were fractionated and subcellular components were assayed for tyrosyl protein kinase activity. About 60% of the kinase activity in the cytoplasm sedimented with the microsomal fraction, whereas 40% remained in the supernatant. Purification of cytosolic and microsomal kinases by ion-exchange and gel filtration chromatography resolved a major species whose molecular mass was 75 kilodaltons (referred to as TPK 75) and a minor one whose molecular mass was greater than 160 kilodaltons. Partially purified TPK 75 phosphorylated a protein of the same molecular mass on tyrosine residues. The activity associated with TPK 75 was not stimulated by growth factors and was sensitive to thiol re-agents.
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PMID:Tyrosyl protein kinases in normal rat liver: identification and partial characterization. 657 68


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