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)

Involvement of serine protease-activation in the generation of cytoplasmic factor(s) that induced NHP-specific protein kinase activity in nuclei in anti-Ig-stimulated cells was described. DFP or PMSF with anti-Ig inhibited the induction of cytoplasmic factor(s), whereas pretreatment of cells with DFP or PMSF without anti-Ig did not show any inhibitory effect on anti-Ig-induced generation of cytoplasmic factor(s). TAME or BAME with anti-Ig inhibited the generation of cytoplasmic factor(s) and the simultaneous addition of TAME or BAME with DFP protected the generation of cytoplasmic factor(s) against the inhibitory effect of DFP, showing the involvement of trypsin-like, arginine-type serine protease in anti-Ig-induced generation of cytoplasmic factor(s). Anti-Ig-stimulated membrane preparations induced cytoplasmic factor(s) in normal cytoplasm. The m.w. of precursor proteins present in resting B cells and active cytoplasmic factor(s) were approximately 150,000 and 45,000, respectively. These results showed that anti-Ig-activated membrane-bound serine protease split precursor proteins in resting B cells into active cytoplasmic factor(s) responsible for signal transmission.
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PMID:Involvement of anti-Ig-activated serine protease in the generation of cytoplasmic factor(s) that are responsible for the transmission of Ig-receptor-mediated signals. 31 62

A tri-, di-, and monoacylglycerol-hydrolyzing enzyme from rat adipose tissue has been detergent-solubilized and separated from monoacylglycerol lipase (H. Tornqvist and P. Belfrage, 1976, J. Biol. Chem. 251, 813-819) and lipoprotein lipase by use of ion-exchange chromatography, broad and narrow pH range electrofocusing and gel chromatography. The final preparation contained several different proteins. One of these, with an apparent minimum molecular weight of 86,000 by SDS-gel electrophoresis, was identified as the enzyme protein of hormone-sensitive lipase: a) the enzyme activity was reproducibly stimulated 50-100% by incubation with cyclic AMP-dependent protein kinase, cyclic AMP and ATP-Mg2+; b) the relative intensity of the Mw 86,000 protein band, and only this, closely paralleled the enzyme activity during narrow pH range electrofocusing and during subsequent gel chromatography of the electrofocusing enzyme peak fraction; c) only the Mw 86,000 protein extensively incorporated 32p from [gamma-32P]ATP after incubation with protein kinase and cyclic AMP. The pI of the enzyme was 6.7, it had the same Stokes radius on Sephadex G 200 as IgG and was 50% inactivated by 10 micron HgCl2, 20 micron PCMB, 50 micron DFP, 10 mM NaF and non-ionic detergents above their critical micellar concentration.
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PMID:Identification and some characteristics of the enzyme protein of the hormone-sensitive lipase from rat adipose tissue. 66 58

Besides its procoagulant activity, thrombin has been shown to stimulate cell proliferation and to regulate the fibrinolytic pathway. We report here the effect of purified human alpha thrombin on the synthesis of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) by cultured human mesangial cells. Thrombin (0 to 2.5 U/ml) increased in a time- and dose-dependent manner the production of t-PA and PAI-1 (2- to 3-fold increase of secreted t-PA and PAI-1 release during a 24 hour incubation). This effect was associated with a twofold increase in DNA synthesis measured by 3H-thymidine incorporation. Zymographic analysis and reverse fibrin autography showed that thrombin also increased the level of the 110 Kd t-PA-PAI-1 complex, whereas PAI-1 was present as a free 50 Kd form in the culture medium conditioned by unstimulated and thrombin-stimulated cells. Free t-PA was never observed. Both membrane binding and catalytic activity of thrombin were required since the effects of 1 U/ml thrombin were inhibited by addition 2 U/ml hirudin, which inhibits the membrane binding and catalytic activity of thrombin, and since DFP-inactivated thrombin, which has the ability to bind but which has no enzymatic activity, did not induce t-PA or PAI-1. Gamma thrombin, which does not bind to thrombin receptor, did not increase t-PA and PAI-1 releases. The effects of thrombin were probably mediated by protein kinase C activation since H7, an inhibitor of protein kinases, inhibited significantly thrombin effects on t-PA and PAI-1 production, and since addition of an activator of protein kinase A, 8-bromocyclic AMP (100 microM), induced a significant inhibition of the thrombin effect. The effects of thrombin were also suppressed by 1.25 micrograms/ml alpha amanitin, suggesting a requirement of de novo RNA synthesis. Northern blot analysis indicated that thrombin induced an increase in the mRNA levels of t-PA and of PAI-1. We conclude that thrombin increases DNA synthesis in human mesangial cells and enhances the synthesis of both t-PA and PAI-1. The latter is released in a large excess as compared to t-PA. Hence, thrombin may have a role in provoking a localized hypofibrinolytic state and may contribute to the persistence of glomerular fibrin deposits during proliferative glomerulonephritis.
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PMID:Thrombin regulates components of the fibrinolytic system in human mesangial cells. 212 90

The mRNA for human hormone-sensitive lipase (HSL) was identified using Northern blot analysis and a cDNA-probe for rat HSL. As in the rat, human adipose tissue expresses a single mRNA species of 3.3 kb. Using Western blotting with a polyclonal rabbit antibody towards rat adipose tissue HSL, the corresponding enzyme in human adipose tissue was identified with an apparent 88 kDa polypeptide, thus slightly larger than the rat and bovine 84 kDa, and the mouse and guinea-pig 82 kDa species. Additional evidence for the identification was provided by the inhibition of HSL diacylglycerol lipase activity by the anti-rat HSL antibody, and by NaF, DFP and Hg2+, known inhibitors of HSL. The concentration of the enzyme, as reflected by its activity per g tissue and the specific activity was about two thirds of that in the rat adipose tissue (200 g rats). The identification of the human enzyme protein made it possible to directly demonstrate its phosphorylation by cAMP-dependent protein kinase, thus extending the previous report regarding activation of the lipase with this kinase and ATP-Mg2+ in human adipose tissue extracts (Khoo, J.C., Aquino, A.A. and Steinberg, D. (1974) J. Clin. Invest. 53, 1124-1131).
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PMID:Human adipose tissue hormone-sensitive lipase: identification and comparison with other species. 255 74

Swine adipose tissue hormone-sensitive lipase, purified 475-fold to 10% protein purity, has been identified as a polypeptide of Mr = 84,000. The enzyme has high specific activity against tri-, di- and monoacylglycerols, as well as cholesterol esters, and is inhibited by millimolar NaF, and micromolar HgCl2 and DFP. The enzyme polypeptide serves as a substrate for cyclic AMP-dependent protein kinase. The characteristics of the hormone-sensitive lipase from swine adipose tissue are similar to those reported previously for the enzyme from rat. They differ from those reported for the lipase from chicken adipose tissue, and possible reasons for these differences are discussed.
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PMID:Hormone-sensitive lipase from swine adipose tissue: identification and some properties. 298 58

Three synthetic irreversible enzyme inhibitors (75 microM di-iso-propylphosphorofluoridate (DFP), 310 microM N alpha-p-tosyl-L-lysine (TLCK) and 240 microM L-1-tosylamide-2-phenylethyl (TPCK) chloromethyl ketone), as well as the transition state analogue chymostatin, inhibit the development of Lewis lung adenocarcinoma (3LL) in C57 BI/6 mice, when 3LL cells are treated once and for a limited period (60 min) prior to grafting. These compounds demonstrate divergent protease specificity and, in the case of TLCK and TPCK, convergent reactivity toward the highly conserved protein kinase catalytic subunit. Using 200 microM chymostatin and low doses (25-40 microM) of the irreversible enzyme inhibitors, the antimetastatogenic effect is revealed to be specific, as primary tumor development is not affected. Although no direct experimental evidence can be forwarded, our results fit with the concept that the motile metastatogenic 3LL cells may constitute a phenotype which, in contrast to the resident cells from the primaries, responds to these enzyme inhibitors in a highly sensitive manner.
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PMID:Decrease of metastatogenic potential by pregraft treatment of Lewis lung carcinoma cells with proteinase and protein kinase affinity labels. 405 8

The cytosolic cholesterol ester hydrolase from bovine corpus luteum has been purified 760-fold, using isoelectric precipitation and gel filtration chromatography, followed by ion-exchange and adsorption chromatographies in the presence of non-ionic detergent. Further purification was achieved by affinity chromatography on triacylglycerol-containing polyacrylamide-agarose. The partially purified enzyme was inhibited by NaF, HgCl2 and DFP. Incubation with [3H]DFP resulted in specific labelling of a polypeptide of Mr = 84000, the same subunit molecular weight as that of the enzyme from adrenal cortex. This Mr 84000 polypeptide from corpus luteum was phosphorylated by the catalytic subunit of cyclic AMP-dependent protein kinase, phosphorylation causing greater than 2-fold activation of the enzyme. Several properties of the cholesterol ester hydrolase from corpus luteum show striking similarities to those of hormone-sensitive lipase from adipose tissue. This provides further evidence that hormone-sensitive lipase, in addition to its role in adipose tissue lipolysis, has a key role in steroidogenic tissues, namely catalysing the supply of free cholesterol from the cholesterol ester stores.
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PMID:Cytosolic cholesterol ester hydrolase from bovine corpus luteum. Its purification, identification, and relationship to hormone-sensitive lipase. 684 67

Diisopropyl phosphorofluoridate (DFP) produces Type I organophosphorus compound-induced delayed neurotoxicity (OPIDN) in adult female chickens. We have proposed that calcium/calmodulin protein kinase II (CaM kinase II) plays a role in the development of OPIDN by increasing the phosphorylation of cytoskeletal proteins. We investigated in vivo the effects of treatment of DFP on CaM kinase II-dependent phosphorylation. In isolated brain supernatants from DFP-treated hens, calmodulin binding increased concurrent with increases in CaM kinase II-dependent autophosphorylation and phosphorylation of cytoskeleton proteins. There were no changes in the relative amounts of the enzyme based on immunobinding studies of antibodies to the CaM kinase II. In the absence of any exogenously added substrate. CaM kinase II and microtubule associated protein-2 (MAP-2) exhibited substantially increased phosphorylation, 833 and 275%, respectively, over brain supernatants from untreated hens. Moreover, isolated brain supernatants from treated hens with exogenously added cytoskeletal proteins and myelin basic protein (MBP) exhibited significant increases in phosphorylation over control, 233, 332 and 60%, for MAP-2, tubulin, and MBP, respectively. 125I-Calmodulin binding studies revealed a 136% increase in calmodulin binding to CaM kinase II in treated hens when compared to control groups. The data suggest that in vivo DFP treatment increases the percentage of unphosphorylated, active CaM kinase II resulting in increased calmodulin binding and subsequent enhanced phosphorylation of cytoskeletal proteins that leads to their aggregation and the production of axonal degeneration.
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PMID:Enhanced calmodulin binding concurrent with increased kinase-dependent phosphorylation of cytoskeletal proteins following a single subcutaneous injection of diisopropyl phosphorofluoridate in hens. 767 40

Diisopropyl phosphorofluoridate (DFP) produces type I organophosphorus ester-induced delayed neurotoxicity in humans and sensitive animal species. This is accompanied by enhanced Ca2+/CaM-dependent protein kinase II (CaM-kinase II) activity, and [125I]calmodulin binding to CaM-kinase II in DFP-treated hen brain supernatant without increase in the enzyme quantity. We have purified CaM-kinase II from control and DFP-treated hen whole brains and compared various physical and biochemical properties. The two enzymes exhibited similar properties in many respects. However, there was a decrease in calcium-independent protein kinase II activity after autophosphorylation, and an increase in K0.5 for free calcium and calmodulin of enzyme purified from DFP-treated hen brains. This change in kinetic parameters may result in greater percentage of total CaM-kinase II present in unphosphorylated form, which is consistent with the increased autophosphorylation of CaM-kinase II and [125I]calmodulin binding in the brain supernatant of DFP-treated hens.
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PMID:Comparison of Ca2+/calmodulin-dependent protein kinase II purified from control and diisopropyl phosphorofluoridate (DFP)-treated hens. 838 10

Diisopropyl phosphorofluoridate (DFP) produces organophosphorus ester-induced delayed neurotoxicity (OPIDN) in humans and sensitive animal species, e.g., adult chicken. The chickens were sacrificed 18 days after a single dose of DFP (1.7 mg/kg, s.c.), which produced severe ataxia or paralysis in 10-14 days. We studied Ca2+/calmodulin-dependent in vitro neurofilament phosphorylation by the brain subcellular fractions of control and DFP-treated hens. There was enhanced phosphorylation of all three NF subunits by the brain supernatant of treated hens. This was accompanied by enhanced autophosphorylation of both Ca2+/CaM-dependent protein kinase II (CaM-kinase II) subunits and increased calmodulin binding using either 125I-CaM or biotinylated calmodulin to only alpha subunit without concomitant increase in the amount of this enzyme. This enhanced phosphorylation of neurofilament subunits was completely and partially inhibited by mastoparan and KN-62, respectively. There was no alteration in the distribution of CaM-kinase II activity in treated hens and the activity was not related to its concentration in different subcellular fractions. The difference in 125I-CaM binding to CaM-kinase II alpha subunit in the brain supernatants of control and DFP-treated hens was not altered by its phosphorylation or dephosphorylation. The increased CaM-kinase II activity in the soluble fraction of DFP-treated hen brain may be involved in the aberrant phosphorylation of axonal neurofilaments, and thus play a role in OPIDN.
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PMID:Neurofilament phosphorylation and [125I]calmodulin binding by Ca2+/calmodulin-dependent protein kinase in the brain subcellular fractions of diisopropyl phosphorofluoridate (DFP)-treated hen. 857 15


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