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

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of spermine on tyrosine hydroxylase (TH) activity purified from bovine adrenal medulla was examined before and after phosphorylation by the catalytic subunit of cyclic AMP-dependent protein kinase (A-kinase). Before phosphorylation, spermine (less than 1 mM) inhibited the enzymatic activity, and negative cooperative effect of spermine on TH (Hill coefficient = 0.7) was observed from the kinetic analysis concerning 6-methyl-5,6,7,8-tetrahydropterin (6MPH4). Spermine interacted noncompetitively toward tyrosine and the Ki for spermine was calculated to be 68 microM. Phosphorylation abolished the ability of spermine to inhibit TH activity in a negative cooperative manner against the pterin cofactor, and also increased four-fold the Ki value against the substrate. These results suggest that spermine may inhibit TH activity by interacting with the pterin binding site of the enzyme molecule in a manner of negative cooperativity, and that this inhibition is reversed by the conformational change of regulatory domain of TH after phosphorylation by A-kinase.
...
PMID:Effect of spermine on tyrosine hydroxylase activity before and after phosphorylation by cyclic AMP-dependent protein kinase. 289 56

Spermine-binding protein (a rat ventral prostatic protein with high affinity for spermine) was phosphorylated in situ through the action of intrinsic cellular protein kinase(s), suggesting it to be a phosphoprotein in vivo. The purified protein served as a substrate in a number of cyclic AMP-independent protein kinase reactions in vitro, but not for cyclic AMP-dependent, Ca2+ + calmodulin-dependent or Ca2+ + phospholipid-dependent protein kinases. Available data indicate that at least one of the cyclic AMP-independent protein kinases (cytosolic protein kinase C2) may be physiologically relevant in mediating the phosphorylation of this protein. The phosphorylation reaction was stimulated several-fold in the presence of spermine. Spermidine was somewhat less effective, whereas putrescine, cadaverine and 1,6-hexanediamine were minimally active. Phospho amino acid analysis of 32P-labelled spermine-binding protein indicated that phosphoserine was the only labelled phospho amino acid. Spermine-binding protein did not undergo autophosphorylation, or modify the stimulative effect of spermine on the phosphorylation of other substrates such as non-histone proteins. In situ the phosphorylation of spermine-binding protein in tissue from castrated rats was markedly diminished as compared with the normal. Since the phosphorylation of spermine-binding protein appears to be mediated by cyclic AMP-independent protein kinase(s) whose activity in the prostate is under androgenic control, it is suggested that androgen-dependent modulation of the protein kinase(s) exerts a regulatory control (via phosphorylation-dephosphorylation) on the spermine-binding activity and stability of this protein in vivo. Further, since this protein is a substrate for only the cyclic AMP-independent protein kinases, it could serve as a tool for the investigation of such kinases.
...
PMID:Polyamine-stimulated phosphorylation of prostatic spermine-binding protein is mediated only by cyclic AMP-independent protein kinases. 299 98

Ornithine decarboxylase, the rate-limiting enzyme in polyamine biosynthesis, has been shown to be regulated in thyroid by thyrotropin both in vivo and in vitro. Little, however, is known of the role of polyamines in thyroid cell function. Since studies in other tissues suggest that polyamines may influence protein phosphorylation, we studied the effect of the polyamines on various protein kinase activities in rat thyroid. Putrescine, spermidine, and spermine inhibit cyclic-AMP-dependent histone H1 kinase activity when measured in the cytosol fraction of rat thyroid; this effect is largely reproduced by NaCl concentrations of equivalent ionic strength. Both spermidine and spermine effect a 1.6-2.4-fold increase in cytosolic cyclic-AMP-independent (messenger-independent) casein kinase activity; stimulation by both polyamines is maximal at 5mM. A similar profile of stimulation is observed for messenger-independent casein kinase activity in crude nuclear preparations. Sodium chloride fails to stimulate both cytosolic and nuclear messenger-independent casein kinase activities at ionic strength equivalent to the spermine concentrations used. Spermine, but not putrescine, spermidine, or sodium chloride, inhibits calcium/phospholipid-dependent protein kinase C activity in cytosol extracts partially purified by DEAE chromatography. These findings suggest that regulation of protein kinase(s) by polyamines may represent a proximal locus (i) of action of thyrotropin-regulated ornithine decarboxylase activity in thyroid.
...
PMID:Differential effects of polyamines on rat thyroid protein kinase activities. 299 43

Microtubule protein prepared by cycles of assembly-disassembly contains a cyclic AMP-dependent protein kinase that phosphorylates the high-molecular-weight microtubule-associated protein MAP-2. The polyamine spermine at 2mM affected the phosphorylation of MAP-2 in a manner that depended on the cyclic AMP concentration. At cyclic AMP concentrations below 10(-6) M, spermine increased the rate of phosphorylation, while at cyclic AMP concentrations above 10(-6) M, spermine decreased the rate of phosphorylation. Spermine also decreased the final extent of cyclic AMP-dependent phosphorylation but did not affect the protein substrate specificity of the microtubule-associated protein kinase. MAP-2 was the principal substrate both in the presence and in the absence of spermine. Because of these results, we propose that microtubule protein phosphorylation may be regulated in vivo by spermine as well as by cyclic AMP levels.
...
PMID:Polyamine regulation of the microtubule-associated protein kinase. 299 32

Spermine or putrescine increased cAMP levels through a catalase-sensitive mechanism, resulting in, most notably, a dephosphorylation of protein A (Mr 45,000, pI 5.15) and protein B (Mr 45,000, pI 4.9) and slightly increased phosphatidylcholine (PC) synthesis in HL60 cells. Exogenous dibutyryl cAMP mimicked the polyamine effects. 12-O-Tetradecanoyl phorbol-13-acetate (TPA) also promoted the protein dephosphorylation and PC synthesis, the effects augmented by R59022 and mimicked by exogenous 1-oleoyl-2-acetylglycerol. The effects of spermine (or dibutyryl cAMP) and TPA on PC synthesis were synergistic. It was suggested that cAMP-dependent protein kinase and protein kinase C might mediate, in an independent but inter-related manner, the effects of polyamines and TPA.
...
PMID:Cyclic AMP-like effects of polyamines on phosphatidylcholine synthesis and protein phosphorylation in human promyelocytic leukemia HL60 cells. Comparison with the effects of phorbol ester. 303 Aug 16

A simple and short purification procedure applicable to casein kinase II has been developed, for fully characterizing the enzyme from calf cerebral cortex cytosol. The procedure consists of four chromatographic steps: DEAE-cellulose, phosphocellulose, phosvitin-Sepharose and ATP-agarose which yields 87% pure casein kinase II. The purified enzyme shows three major bands with apparent molecular masses of 42, 38, and 27 kDa by polyacrylamide gel electrophoresis in sodium dodecyl sulfate and is self-autophosphorylated on its 27 kDa polypeptide. The enzyme shows all the characteristics described for casein kinase II from other sources: it is independent of cyclic nucleotides, calcium/phospholipids, and double-stranded poly(I).poly(C); it can utilize both ATP and GTP as phosphoryl donors and can phosphorylate both casein and phosvitin but not histone. The kinetic studies establish that the Km for ATP is 12.5 microM and 25.1 microM when using phosvitin and casein respectively as phosphoryl acceptors. The Km for phosvitin is 0.91 mg/ml and for casein 1.43 mg/ml, while the Vmax is 315 nmol/min/per mg protein and 479 nmol/min/per mg protein for phosvitin and casein respectively. The activity of the kinase is highly stimulated by KCl or NaCl, and almost completely inhibited by heparin concentrations of 1 microgram/ml (92%). This inhibition is reduced to only 33% in the presence of optimal KCl concentrations (150 mM). Spermine stimulates enzyme activity, whilst hemin produces a slight inhibition.
...
PMID:An improved purification procedure and properties of casein kinase II from brain. 322 65

1. Triton extracts of syncytiotrophoblast membranes were incubated with [gamma-32P]ATP, MgCl2 and MnCl2. Addition of epidermal growth factor (EGF) resulted in increased phosphorylation not only of the EGF receptor and a Mr-35,000 protein as previously described, but also a protein of Mr 95,000 on both tyrosine and serine residues. In addition, a small increase in the phosphorylation of a protein of Mr 105,000 was observed. Spermine had a similar effect on the phosphorylation of the Mr-95,000 protein, without affecting the phosphorylation of the other proteins. In the absence of MnCl2, the effect of spermine on the phosphorylation of Mr-95,000 protein was still evident, whereas that of EGF was greatly diminished. 2. The Mr-95,000 protein bound poorly to wheat-germ-lectin-Sepharose and was not precipitated by antisera specific for insulin and EGF receptors. The protein continued to exhibit serine and tyrosine phosphorylation on addition of [gamma-32P]ATP, MgCl2 and MnCl2 to a glycoprotein-depleted fraction prepared by chromatography on wheat-germ-lectin-Sepharose. The extent of phosphorylation was no longer increased by spermine or EGF, but was inhibited by heparin. 3. It is suggested that the Mr-95,000 protein not only is a possible direct substrate for the EGF-receptor (but not the insulin receptor) tyrosine kinase but is a substrate for other endogenous kinases, including a protein tyrosine kinase which is probably not a glycoprotein, and a protein serine kinase with properties similar to those of casein kinase II.
...
PMID:Epidermal growth factor, but not insulin, stimulates tyrosine phosphorylation of an endogenous protein of Mr 95,000 in triton extracts of human placental syncytiotrophoblast membranes. 332 13

Subcellular fractions prepared from rodent forebrain at different postnatal ages were examined for calmodulin-binding proteins using [125I]calmodulin and a gel overlay technique. Synaptic junction (SJ) fractions from newborn brain, which display purity comparable to adult SJ fractions, contain low but detectable amounts of 60 and 50 kdalton calmodulin-binding polypeptides; the latter being the major postsynaptic density protein. These polypeptides have recently been shown to be the calmodulin-binding protein subunits of calmodulin-dependent protein kinase II (CaM-kinase II). CaM-kinase II polypeptides represented the predominent calmodulin-binding proteins in nearly every subcellular fraction examined, regardless of postnatal age. Large increases were observed in the CaM-kinase II content of every subcellular fraction throughout postnatal development. During development, a striking shift in the subcellular distribution of CaM-kinase Ii was observed. Over 4 times as much CaM-kinase II was cytosolic relative to particulate in newborn brain while this ratio was completely reversed in adult brain. Large age-dependent increases in particulate-associated CaM-kinase II were observed in highly purified synaptic plasma membrane (5-fold) and SJ (14-fold) fractions. The CaM-kinase II content of SJ fractions increased approximately 70% between days 24 and 90, a period in development that follows the most active stages of synapse formation in situ. In adult brain, approximately 60% of CaM-kinase II in crude synaptosomal fractions (P2-INT) was recovered in SJ fractions. The CaM-kinase II in SPM fractions from all developmental ages resists solubilization in Triton X-100 and greater than 90% is recovered in SJ fractions. These studies indicate that during brain development the accumulation of SJ-associated CaM-kinase II represents an important process in the molecular and enzymatic maturation of CNS postsynaptic structures.
...
PMID:Changes in the subcellular distribution of calmodulin-kinase II during brain development. 398 14

Purified casein kinase G was found able to catalyse the synthesis of [gamma-32P]ATP in the presence of ADP, phosphocasein (previously 32P-labeled by the forward kinase reaction) and magnesium. Apparent Km values of approx. 0.5 mM for phosphocasein and 7.5 mM for ADP were calculated, these values indicating low affinities for the substrates as compared to those exhibited for casein and ATP in the forward reaction. The reverse casein kinase G activity appeared to prefer ADP and GDP as phosphate acceptors. Whereas the casein kinase G reverse reaction could be supported by casein, phosvitin and histone previously phosphorylated by the enzyme, the same proteins could not serve as a phosphate source when previously phosphorylated by the cAMP-dependent protein kinase. Forward and reverse casein kinase G reactions exhibited different optimal pH values (8.5 and 7.2, respectively) and a different sensitivity to Mg2+. Spermine, which activated the kinase activity, blocked the reverse reaction at millimolar concentrations. Although the biological significance of the casein kinase G reverse activity remains to be assessed in intact cell, the process may be useful as a tool in the characterization of phosphorylatable sites in phosphoproteins.
...
PMID:Reversibility of the phosphate transfer between ATP and phosphoproteins catalysed by a cyclic nucleotide independent (G type) casein kinase. 657 5

The effects of polyamines on the catalytic activity of casein kinase II have been studied. Of the three polyamines tested (putrescine, spermidine, and spermine), spermine was the most effective at stimulating the enzyme. When physiological concentrations of potassium and magnesium were utilized, 50% activation was observed at 0.28 mM spermine or 0.70 mM spermidine. With mixtures of spermine and spermidine at physiological concentrations for the reticulocyte (0.04 and 1.06 mM, respectively), a 2.5-fold stimulation of casein kinase II activity was observed. In general, stimulation of the enzyme was dependent on salt concentration and it was necessary to hold ionic strength constant in order to separate specific activation by the polyamines from general salt activation. Optimum activation by polyamines was observed at low ionic strength and physiological concentrations of Mg2+. When beta-casein and eukaryotic initiation factors 2 or 3 were used as substrates, up to 3.5-fold stimulation of casein kinase II was observed. In the absence of polyamine, half-saturation of the enzyme by Mg2+ was observed at 1-3 mM MgCl2, a concentration much higher than required for ATP-Mg2+ complex formation. This dependence of the enzyme on Mg2+ was greatly diminished in the presence of spermine. Spermine decreased the apparent Km for casein and increased the maximum velocity of the reaction. Spermidine and spermine also effectively reversed inhibition by 2,3-bisphosphoglycerate. The significant activation by polyamines observed under conditions similar to those measured for the red cell suggest that the polyamines, spermidine and to a lesser extent spermine, function to regulate casein kinase II in vivo.
...
PMID:Kinetics of activation of casein kinase II by polyamines and reversal of 2,3-bisphosphoglycerate inhibition. 658 24


<< Previous 1 2 3 4 5 Next >>

---