Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Protamine Kinase”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 433 records · Page 24Linked to original sources
PubMed1975

Nuclear protein-kinase activity in perfused rat liver stimulated with dibutyryl-adenosine cyclic 3':5'-monophosphate.

Cytoplasmic and nuclear protein kinase activities from perfused rat liver have been studied in response to dibutyryl-adenosine cyclic 3':5'-monophosphate added at a concentration that stimulates hepatic gluconeogenesis (100 muM). Total nuclear protein kinase, as assayed using a mixed histone fraction as phosphate acceptor, is increased by 5-fold within 8 min of the addition of cyclic nucleotide to the perfusate. In contrast the total cytoplasmic protein kinase activity is decreased to 50% of the control value. The protein substrate specificity of the protein kinase that is present in the nucleus in response to dibutyryl-adenosine cyclic 3':5'-monophosphate stimulation is similar to that of cytoplasmic, adenosine cyclic 3':5'-monophosphate-dependent, protein kinase but is distinct from that of the enzyme(s) present in control nuclei. The predominant species to protein kinase from stimulated nuclei has a sedimentation constant of 3.9 S. This value is identical to that of the catalytic subunit of cytoplasmic adenosine 3':5'-monophosphate-dependent protein kinase. These data suggest that some of the effects of adenosine 3':5'-monophosphate on nuclear events may be mediated through its interaction with the inactive protein kinase holoenzyme in the cytoplasm and the subsequent redistribution of the active catalytic subunits generated by this interaction.

Animals↗
PubMed1991

Stimulation of a histone H4 protein kinase in Triton X-100 lysates of rabbit peritoneal neutrophils pretreated with chemotactic factors: effect of leukotriene B4 and cytochalasin B.

The effects of leukotriene B4 on the stimulation of a histone H4 kinase activity in rabbit peritoneal neutrophils have been studied. LTB4 activated the kinase within 10 sec with the increasing activity decaying to near basal level after 20 sec of stimulation. The effect was not inhibited by removal of extracellular calcium or loading the cells with quin-2/AM. Pretreatment of the cells with cytochalasin B greatly enhanced and prolonged the activation of the kinase. Pretreatment of the cells with LTB4 or fMet-Leu-Phe inhibited the effect of the later addition of LTB4. Since similar characteristics of LTB4 and cytochalasin B have also been observed in LTB4-stimulated responses such as secretion and superoxide generation, the results suggest a potential role of H4 kinase in LTB4-stimulated responses.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1986

Kinetic properties of the insulin receptor tyrosine protein kinase: activation through an insulin-stimulated tyrosine-specific, intramolecular autophosphorylation.

The insulin receptor is an insulin-activated, tyrosine-specific protein kinase. Previous studies have shown that autophosphorylation of tyrosine residues on the Mr 95,000 is associated with an activation of the protein kinase activity toward exogenous protein substrates. We have employed the highly purified insulin receptor, immobilized on insulin-Sepharose or eluted in an active form, to define the metal/ATP requirements for kinase activation, the relationship of receptor autophosphorylation to activation, and the kinetic properties of the autophosphorylated, activated receptor kinase. Prior incubation of the immobilized receptor with 2 mM ATP, 10 mM Mg (or 10 mM Mn), followed by removal of these reactants, served to abolish the upward curvilinearity in the rate of histone 2b (tyrosine) phosphorylation measured subsequently. This treatment also markedly increased the rate of histone 2b phosphorylation as compared to that observed with the unmodified, immobilized receptor, as estimated under conditions that per se minimized further activation. The extents of maximal activation of receptor histone 2b (tyrosine) kinase obtained on preincubation with MgATP or MnATP are identical; however, the affinity of the receptor for MnATP is approximately 10-fold higher than that for MgATP. The higher affinity of the receptor for MnATP is observed for both autophosphorylation/autoactivation and histone 2b tyrosine kinase activity (Km MnATP approximately 0.01 mM; Km MgATP approximately 0.1 mM). Autophosphorylation/autoactivation per se does not significantly alter the apparent affinity for MeATP (or protein substrate, as previously reported) but increases Vmax. Activation of receptor histone 2b (tyrosine) kinase is due to tyrosine-specific autophosphorylation of the Mr 95,000 (beta) subunit; thus the extent of total 32P incorporation into the beta subunit correlates precisely with the extent of kinase activation, both over time and at a wide variety of Me2+ ATP concentrations. Sequential treatment of the autophosphorylated receptor with elastase and trypsin yields a single, basically charged 32P-peptide, Mr less than 2000. The functional properties of the unphosphorylated and fully phosphorylated receptor were compared after elution from insulin-Sepharose. The insulin binding characteristics of the two forms of the receptor were indistinguishable; the kinase properties differed greatly; whereas the histone 2b activity of the unphosphorylated receptor was low in the basal state, and activated 10-fold by insulin, the fully autophosphorylated receptor exhibits maximal histone 2b kinase in the basal state and is unaffected by insulin addition.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1976

Protein kinases and their substrates in brown adipose tissue from newborn rats.

The 10000 X g supernatant fraction of brown fat from newborn rats catalyzed the cyclic AMP-dependent phosphorylation of both histone and a preparation of proteins from the same subcellular fraction (endogenous proteins). The apparent affinity for ATP was lower for the phosphorylation of the endogenous proteins than for the phosphorylation of histone. In order to discover whether the phosphorylation of histone and the endogenous proteins were catalyzed by different enzymes, the 100000 X g supernatant was fractionated by ion-exchange and adsorption chromatography. Three different cyclic AMP-dependent protein kinases and one cyclic AMP-independent protein kinase were separated and partially purified. Each of these enzymes catalyzed the phosphorylation of both substrates, and the difference in apparent Km for ATP remained. Neither affinity chromatography on histone-Sepharose, nor electrophoresis on polyacrylamide gels resulted in the separation of the phosphorylation of histone from that of the endogenous proteins of any of the partially purified kinases. Moreover, experiments in which the phosphorylated substrates were separated by differential precipitation with trichloroacetic acid showed that the endogenous proteins competitively inhibited the phosphorylation of lysine-rich histone. It is concluded that each of the partially purified kinase preparations contains protein kinase, which catalyzes the phosphorylation of both substrates. The difference in apparent Km for ATP was found to be due to the presence in the endogenous protein preparation of a low molecular weight compound which competes with ATP. This was not ATP nor the modulator protein. The ratio of the phosphorylation of endogenous proteins to that of histone was much higher for the cyclic AMP-independent kinase preparation than for the other enzymes. Electrophoresis of the endogenous substrates in the presence of sodium dodecyl sulphate showed that the enzyme phosphorylated a greater number of proteins than did the cyclic AMP-dependent kinases. The phosphorylation of endogenous proteins relative to that of histone was significantly lower for one of the cyclic AMP-dependent kinases than for the other two. This difference was not reflected in a different pattern of phosphorylation of the individual proteins of the endogenous mixture.

Adenosine Triphosphate↗
PubMed1986

Anticarcinogenic effect of retinoids on 7,12-dimethylbenz(a)anthracene-induced mammary tumor induction, and its relationship to cyclic AMP-dependent protein kinase.

Administration of 13-cis retinoic acid and N-(4-hydroxyphenyl) retinamide daily in the diet to female Sprague-Dawley rats beginning one day after intubation with 7,12-dimethylbenz(a)anthracene (DMBA) prolonged the latency periods and inhibited the percentage incidence of mammary tumors. A significant reduction in the total number of tumors was also evident. The inhibition of mammary tumor growth by retinoids was associated with a significant increase (3-fold) in cytosolic cAMP-binding and histone kinase activities. The increase of histone kinase activity was almost totally in the cAMP-dependent protein kinase Type II. Retinoic acid increased the amount of the regulatory subunit (R11) rather than altering its cAMP binding affinity. These results suggest that cAMP-dependent protein kinase Type II may be involved in mediating the retinoid action in the inhibition of mammary tumor growth in vivo.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Cyclic activation of histone H1 kinase during sea urchin egg mitotic divisions.

Fertilized sea urchin eggs undergo a series of rapid and synchronized mitotic divisions. Extracts were made at various times throughout the first three mitotic divisions and assayed for phosphorylating activity toward histone H1. Histone H1 kinase (HH1K) undergoes a transient activation (8- to 10-fold increase) 20 min before each cleavage. The amplitude of the HH1K peak strongly depends on the synchrony of the egg population. Concomitant cytological observations show that the time-course of HH1K correlates with the time-course of nuclear envelope breakdown and of metaphase. This correlation is observed at each cell division cycle. HH1K from each of the three first mitoses show identical time- and concentration-dependence curves as well as identical dose-inhibition curves with 6-dimethylaminopurine and quercetin, suggesting that the same (group of) kinase(s) is (are) activated before each cleavage. Ionophore A23187 does not trigger, but inhibits, HH1K activation; however, partial activation of the eggs with ammonia at pH 9.0 (but not at pH 8.0) triggers the transient HH1K activation. Appearance of the HH1K cycle requires protein synthesis since it is completely abolished in emetine-treated eggs. Although cytochalasin B blocks egg cleavage, it does not inhibit HH1K activation nor nuclear divisions. A prolonged HH1K activation cycle is observed in eggs arrested in metaphase with colchicine or nocodazole. Despite the existence of a cycle in cAMP concentration during mitosis, forskolin, an activator of adenylate cyclase, does not modify the time-course of HH1K activation and of cell division. The cycling HH1K is independent of calcium-calmodulin, calcium-phospholipids, or cyclic AMP. It clearly resembles the mammalian "growth-associated histone kinase." The relationship between the transient activation of HH1K and the intracellular mitotic factors driving the cell cycle is discussed.

Ammonium Chloride↗
PubMed1982

Insulin activates a tyrosine-specific protein kinase in extracts of 3T3-L1 adipocytes and human placenta.

Insulin activates a tyrosine-specific cAMP-independent protein kinase when added directly to detergent extracts of differentiated 3T3-L1 adipocytes and humal placental membranes. The kinase is also activated by antibody to the insulin receptor and, to a lesser extent, by proinsulin. It catalyzes the phosphorylation of the 92,000-dalton component of the insulin receptor, histone, and casein; in each case, tyrosine is the principal amino acid modified. Under the conditions used to activate the kinase, insulin does not affect the rate of dephosphorylation of the receptor or of histone. The insulin-activated kinase is copurified with the human placental insulin receptor until the final elution from insulin-Sepharose. It remains to be established whether the kinase and the insulin receptor are separate molecules.

Adipose Tissue↗
PubMed1975

Regulation of adenosine 3:5-monophosphate-dependent protein kinase.

The effects of epinephrine, glucagon, insulin and 1-methyl-3-isobutylxanthine on adenosine 3:5-monophosphate (cAMP)-dependent protein kinase activity were investigated in the perfused rat heart. The conditions for homogenization of heart tissue and assay of protein kinase are described. The activation state of the enzyme is expressed as the ratio of the rate of phosphorylation of histone in the absence to that in the presence of 2 mu-M cAMP. This activity ratio is stable in crude homogenates over 15 min of incubation; it is not affected by up to 30-fold dilution of the tissue volume. The ratio is elevated to a variable degree in hearts taken immediately from the animal but falls to a stable, basal level of 0.15 to 0.20 after 15 min of perfusion in vitro. An optimal concentration of epinephrine (10 mu-M) in the perfusate elevates cAMP from 0.5 to 1.3 nmol per g of tissue and increases the protein kinase activity ratio from 0.20 to 0.65. When hearts are perfused with a steady, submaximal concentration of epinephrine (0.4 mu-M), the level of cAMP and the protein kinase activity ratio rise in parallel within 15 s and remain elevated for at least 10 min. When epinephrine is removed from the perfusion medium, the level of cAMP and enzyme activity ratio decline rapidly to basal levels. Both glucagon and the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine also increase the cardiac cAMP levels and protein kinase activity ratio in a dose-dependent manner. Glucagon acts as rapidly as does epinephrine whereas 1-methyl-3-isobutylxanthine requires at least 30 s before any effect can be observed. Insulin by itself does not significantly affect the cyclic nucleotide level or enzyme activity. The hormone has not been observed to lower the cAMP level or protein kinase activity in the heart under any conditions tested. In concentrations of 10 microunits per ml or greater, it does, however, cause a slight rise in the tissue level of cAMP and the protein kinase activity when these have been elevated to intermediate levels by exposure to epinephrine. This effect could only be observed when hearts were treated with catecholamine and could not be detected with glucagon or 1-methyl-3-isobutylxanthine. In all cases tested, slight increases in the protein kinase activity ratio (from 0.2 to 0.3) were accompanied by much greater increases in the amount of phosphorylase in the a form (20% to 70%). It was observed that at perfusion times greater than 3 min, there was a significant reduction in phosphorylase activity even though both the cAMP level and protein kinase activity remained elevated. In these studies, changes in the protein kinase activity correlate well with the tissue cAMP levels under all conditions tested.

Adenosine Triphosphate↗
PubMed1987

Insulin increases membrane protein kinase C activity in rat diaphragm.

Calcium/phospholipid-dependent protein kinase activity (protein kinase C) was identified in rat diaphragm membrane and cytosol fractions by means of in vitro phosphorylation either of histones or of a specific 87 kDa protein substrate, combined with phosphopeptide-mapping techniques. Both insulin and tumor-promoting phorbol ester treatment of the diaphragm preparations led to increased protein kinase C activity in the membrane fractions. In contrast to the phorbol ester, however, insulin did not induce a concomitant decrease in cytosolic activity, indicating that translocation of the enzyme had not taken place. Thus, insulin appears to increase specifically membrane protein kinase C activity in rat skeletal muscle, possibly through a mechanism not identical to that induced by phorbol esters.

Animals↗
PubMed1981

Cyclic AMP-binding capacities and histone kinase activation in subcellular components of neocortical tissue. Differential responses to three neurohumoural agents.

1. Noradrenaline and histamine, when added to superfused guinea-pig cerebral-cortical tissues, increased both cyclic AMP-dependent and -independent histone kinase activities of some, but not of all, subsequently isolated subcellular fractions, and decreased their cyclic [(3)H]AMP-binding capacity, which was concluded to be due to an increase in endogenously bound cyclic AMP. 2. Adenosine and 2-chloroadenosine also diminished the cyclic [(3)H]AMP-binding capacities, but did not affect the histone kinase activities. 3. DEAE-cellulose chromatography and stability to KCl additions showed that the greater part of the histone kinase of the present preparations corresponded to the type II enzyme [of Corbin, Keely & Park (1975) J. Biol. Chem.250, 218-225], with a lesser amount of type I activity. Different sites of cyclic AMP accumulation in relation to these or other kinases are considered in interpreting the differential tissue responses to the neurohumoural agents examined.

Adenosine↗
PubMed1983

Protein kinase activity associated with a phorbol ester receptor purified from mouse brain.

Protein kinase activity copurified with the receptor for 12-O-[3H]tetradecanoylphorbol-13-acetate during its purification from mouse brain particulate protein. All attempts to resolve the protein kinase activity from the receptor were unsuccessful. The isolated receptor required phospholipid and divalent calcium for maximal protein kinase activity. The protein kinase was not activated by cyclic nucleotides or calmodulin. There are striking similarities between the receptor-associated protein kinase activity and the calcium- and phospholipid-dependent protein kinase, which has been suspected of mediating the effects of biological stimuli associated with increased phosphatidylinositol turnover.

Animals↗
PubMed1984

Phosphorylation of H1 subtypes in regenerating rat liver.

H1 histone of rat liver consists of four molecular species designated as H1-1, -2, -3, -4. After partial hepatectomy, phosphorylation of H1-3 was induced first, occurring even within 15 h after the operation. By partial hepatectomy, the rate of incorporation of [3H]lysine into H1 histone increased an average of 4-5 times, but that into H1-4 increased 16-20 times. This actively synthesized H1-4 was subsequently degraded rapidly. Thus induction of this active turnover of H1-4 seems to be correlated with liver regeneration. The maximum activity for phosphorylation of H1-3 attained in regenerating liver was five times that in normal liver. By 36 h after the operation, the phosphorylated peak in the chromatographic pattern had moved forward to a position between the peaks of H1-2 and H1-3, named H1-3'. The newly synthesized H1-3 was not transferred appreciably to H1-3' within 30 h after the operation. At 48 h after the operation, H1-3' amounted to 40% of the total H1-3 subtype. The specificity of the phosphorylation reaction was examined in a reaction system consisting of isolated H1 histone and cAMP-dependent kinase. It was concluded that the specificity of the phosphorylation reaction in vivo was due mainly to the difference in structures of different H1 subtypes.

Animals↗
PubMed1993

Activation of a histone H1 kinase by tyrosine phosphorylation in v-src-transformed fibroblasts.

Using anti-phosphotyrosine immunoaffinity chromatography, we have searched for serine/threonine kinases that are directly regulated by tyrosine phosphorylation in v-src-transformed rat 3Y1 fibroblasts. Tyrosine phosphoprotein preparations from v-src-transformed cells contain a kinase activity that phosphorylates histone H1 in vitro on serine residues and this activity is present at a 20-fold greater level than that in parental cell preparations. This activity elutes from a MonoQ FPLC column as a single peak and gel filtration chromatography suggests that the kinase has a molecular mass of approximately 55 kDa. Tyrosine phosphatase treatment inactivates the histone H1 kinase and this result indicates that the specific activity of the kinase is regulated by tyrosine phosphorylation. Experiments with cells transformed with a temperature-sensitive mutant of the v-src oncogene demonstrate that the tyrosine phosphorylation of the histone H1 kinase is an early event in v-src transformation. The kinase is distinct from known cdc2 family members that contain the PSTAIR motif, because the kinase can be separated almost completely from these proteins by immunoprecipitation with an antibody against p34cdc2. The profile of antibody reactivity and sensitivity to modulators of protein kinases suggests that this activity is distinct from known second messenger-regulated kinases and from previously characterized MAP kinases.

Amino Acid Sequence↗
PubMed1989

A 60 kd cdc2-associated polypeptide complexes with the E1A proteins in adenovirus-infected cells.

p60 is a cellular protein that binds to the adenovirus E1A protein complex in virally infected or transformed human cells. In both infected and uninfected cells, p60 was found in a complex with the cdc2 protein kinase. Immune complexes containing p60 and cdc2 display a cell cycle-dependent histone H1 kinase activity that is most active in interphase. The previously described cdc2-p62/cyclin complex also acts as a histone H1 kinase but is maximally active in mitotic metaphase. The shift in the timing of activation of different cdc2-containing complexes suggests that each might play a distinct role in regulation of the cell cycle.

Adenovirus Early Proteins↗
PubMed1995

Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins.

Studies of the temperature-sensitive cdc37-1 mutant of Saccharomyces cerevisiae suggest that Cdc37 is required for passage through the G1 phase of the cell cycle, but its precise function is not known. We have investigated the role of Cdc37 in the regulation of the cyclin-dependent protein kinase Cdc28. We find that G1 arrest in the cdc37-1 mutant is accompanied by a decrease in the Cdc28 activity associated with the G1 cyclin Cln2. This defect appears to be caused by a decrease in the binding of Cdc28 and Cln2. cdc37-1 mutants also exhibit a defect in the binding and activation of Cdc28 by the mitotic cyclin Clb2. Thus Cdc37 may be a regulator that is required for the association of Cdc28 with multiple cyclins.

Base Sequence↗
PubMed1995

Properties of a resiniferatoxin-stimulated, calcium inhibited but phosphatidylserine-dependent kinase, which is distinct from protein kinase C isotypes alpha, beta 1, gamma, delta, epsilon and eta.

We have separated a resiniferatoxin-stimulated histone-kinase activity from human neutrophils, elicited mouse macrophages and murine alveolar macrophages by hydroxyapatite chromatography. The assay conditions for resiniferatoxin kinase were optimized as part of this study and in the presence of phosphatidylserine but absence of Ca2+ the Ka for histone IIIs phosphorylation by resiniferatoxin was calculated as 16 nM. Using a phosphate gradient of 20-500 mM, peaks of protein kinase C activity could be washed from the hydroxyapatite column in 300 nM phosphate and resiniferatoxin kinase recovered in 500 mM phosphate. At the optimum concentration of 160 nM, the ability of resiniferatoxin to induce enzyme activity was compared with a range of phorbol esters all at the same concentration. These related compounds failed to activate resiniferatoxin kinase although they have previously been shown to activate protein kinase C isotypes. Similarly sn-1,2,-dioleoylglycerol and the potent irritant capsaicin at 30 microM failed to activate the kinase. A Scatchard analysis of [3H] phorbol dibutyrate binding produced a linear plot (Kd 41.6 nM; Bmax 11.6 fmol unit-1) and binding was inhibited by resiniferatoxin and 12-O-tetradecanoylphorbol-13-acetate (TPA), with resiniferatoxin 700 times more potent than TPA in this respect. A radiolabelled resiniferatoxin binding assay was also used to demonstrate specific binding of [3H]resiniferatoxin which could be inhibited by unlabelled compound. Resiniferatoxin kinase activity was shown to be distinct from the protein kinase C isotypes alpha, beta 1, gamma, delta and epsilon by means of immunological analysis and from the eta isotype, because that isotype was not stimulated by resiniferatoxin but was stimulated by TPA when a pseudosubstrate was used. In addition the resiniferatoxin-stimulated activity was inhibited in-vitro by the addition of Ca2+ (Ki 0.1-0.5 nM free Ca2+). Further purification of resiniferatoxin kinase by Superose chromatography indicated a major activity fraction of about 70-90 kDa. Thus resiniferatoxin kinase, isolated from human and mouse inflammatory cells is distinct from the known isotypes of protein kinase C and is a major resiniferatoxin receptor.

Animals↗
PubMed2006

Histone modifications and the chromatin scaffold for meiotic chromosome architecture.

Chromosomes are capable of remarkable structural adaptability that enables their diverse functions. Histone modifications play pivotal roles in conferring structural diversity to chromosomes by influencing the compactness of chromatin. Several multi-protein complexes bind to chromatin and affect chromosome dynamics, including cohesin, condensin, the chromosome passenger complex, and the synaptonemal complex. The roles of these complexes in promoting chromosome functions include cohesion, condensation and synapsis. It is now crucial to define the relationship between the protein complexes that affect chromosome architecture and the underlying state of the chromatin. During meiosis chromosomes undergo striking morphological changes, including alignment of homologous chromosomes, double-strand break formation and repair, and establishment of meiosis-specific chromosome structures. These dynamic chromosome arrangements are accompanied by the recruitment and expulsion of multi-protein complexes from chromatin. Meiotic chromosome dynamics ensure proper chromosome segregation and production of healthy gametes. Meiosis thus affords an excellent opportunity to determine how histone modifications impact higher order chromosome dynamics by affecting localization and function of chromosome protein complexes. A meiotic mutation in the Drosophila histone kinase, NHK-1, uncovered a critical requirement for histone modifications in chromosome architecture, underscoring the power of this approach.

Animals↗
PubMed1993

Kinetics of MPF and histone H1 kinase activity differ during the G2- to M-phase transition in mouse oocytes.

Maturation promoting factor (MPF) is universally recognized as the biological entity responsible for driving the cell cycle from G2- to M-phase. Histone H1 kinase activity is widely accepted as a biochemical indicator of p34cdc2 protein kinase complex activity and therefore MPF activity. In this paper we present results which indicate that during the G2- to M-phase transition in mouse oocytes the dynamic of p34cdc2 related histone H1 kinase activity differs markedly from the biological activity of MPF as measured by classical cell fusion procedures. MPF is activated just before germinal vesicle breakdown (GVBD) whereas histone H1 kinase is activated 5-7 h later coincident with the formation of the definitive first metaphase plate. The biological activity of MPF is merely reduced to about 50% of control levels by a short period of protein synthesis inhibition (1-2 h) and completely suppressed after a prolonged period of inhibition (4-5 h). By contrast, inhibition of protein synthesis in mouse oocytes results in a rapid and complete suppression of histone H1 kinase activity. Therefore, biological MPF and histone H1 kinase activity should not be used in an interchangeable manner during the G2- to M-phase transition in mouse oocytes.

Animals↗