Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.17 (CaMKII)
 4,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Poly (ADP-ribose) synthetase from bovine thymus was phosphorylated effectively by protein kinase C in vitro. The phosphorylation was dependent on the activators of this kinase, Ca2+ and phospholipid. The apparent Km for the synthetase was about 8 microM, which was lower than that for histone H1. Though the synthetase was a weak substrate for Ca2+/calmodulin-dependent protein kinase II, other protein kinases, cyclic AMP-dependent and cofactor-independent protein kinases did not phosphorylate the synthetase. Phosphorylation of the synthetase by protein kinase C resulted in appreciable inhibition of the synthetase activity.
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PMID:Poly (ADP-ribose) synthetase is phosphorylated by protein kinase C in vitro. 312 Jul 11

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

Tyrosine-specific protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) activity was measured in normal human nonadherent peripheral blood lymphocytes using synthetic peptide substrates having sequence homologies with either pp60src or c-myc. A high level of tyrosine-specific protein kinase activity was found associated with the cell particulate fraction (100 000 X g pellet). High-pressure liquid chromatography and phosphoamino acid analysis of the synthetic peptide substrates substantiated the phosphorylation of tyrosine residues by the particulate fraction enzyme. The human enzyme was also capable of phosphorylating a synthetic random polymer of 80% glutamic acid and 20% tyrosine. Enzyme activity was half-maximal with 22 microM Mg X ATP and had apparent Km values for the synthetic peptides from 1.9 to 7.1 mM. The enzyme preferred Mg2+ to Mn2+ for optimal activity and was stimulated 2-5-fold by low levels (0.05%) of some ionic as well as non-ionic detergents including deoxycholate, Nonidet P-40 and Triton X-100. The enzyme activity was not stimulated by N6;O2'-dibutyryl cyclic AMP (100 microM), N6;O2'-dibutyryl cyclic GMP (100 microM), Ca2+ (200 microM), insulin (1 microgram/ml) or homogeneous human T-cell growth factor (3 micrograms/ml) under the conditions used. Alkaline-resistant phosphorylation of particulate proteins in vitro revealed protein bands with Mr 59 000 and 54 000 suggesting that there are endogenous substrates for the human lymphocyte tyrosine protein kinase.
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PMID:High tyrosine-specific protein kinase activity in normal human peripheral blood lymphocytes. 403 88

After bacteriophage T7 infection, a protein kinase (EC 2.7.1.37; ATP:protein phosphotransferase) activity can be demonstrated in E. coli in vivo by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Cell-free extracts catalyzed the transfer of the terminal phosphoryl group of [(gamma)-(32)P]ATP to endogenous protein acceptor or to added histone. The bond between phosphate and protein shows the characteristics of serine phosphate: it is stable in 1 N HCl (100 degrees ) and cleaved by 1 N KOH (37 degrees ) and by alkaline phosphatase treatment. Moreover, after partial acid hydrolysis, radiophosphate migrates with marker O-phosphoserine on polyethyleneimine-cellulose thin-layer chromatograms. Enzyme activity in uninfected cells is negligible. Ultraviolet irradiation of the phage genome prevents the appearance of the protein kinase; irradiation of the host genome does not. The enzyme activity occurs 4 min after infection and its gene maps in the early region (promoter proximal to gene 1). Ribosomal proteins are phosphorylated in vivo and are substrates in vitro. Enzyme activity in vitro is not changed by addition of cyclic AMP or cyclic GMP.
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PMID:Protein kinase induction in Escherichia coli by bacteriophage T7. 459 95

It has been difficult to establish whether cyclic AMP-mediated protein phosphorylation in nerve cells plays a specific role in synaptic transmission. This difficulty can be overcome in higher invertebrates because their large neurons allow the injection of protein molecules into the cell. We have used intracellular injection to study whether protein phosphorylation is involved in the mechanism of sensitization, a simple form of learning. Sensitization of the gill-withdrawal reflex in Aplysia involves enhancement of transmitter release by presynaptic facilitation at a particular set of synaptic connections between identified sensory neurons and their follower cells. We have found that injection of the catalytic subunit of cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) purified from bovine heart mimics the action of the natural transmitter and of serotonin, the putative transmitter, by simulating the physiological changes that accompany presynaptic facilitation. Intracellular injection of the kinase into a sensory cell (i) broadens the action potential in the presence of tetraethylammonium, indicating an increase in Ca2+ current, (ii) decreases the input conductance of the cell, presumably as a result of a decrease in the K+ current, and (iii) increases the amount of transmitter released by terminals of the sensory cell onto follower neurons.
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PMID:Intracellular injection of t he catalytic subunit of cyclic AMP-dependent protein kinase simulates facilitation of transmitter release underlying behavioral sensitization in Aplysia. 611 94

The activation state of cyclic AMP-dependent protein kinase(s)(ATP:protein phosphotransferase, EC 2.7.1.37) is transiently increased 2-fold as a function of G1 progression in mitotically synchronized Chinese hamster ovary cells. The cellular content of type I kinase increases concomitantly with the increase in general protein, whereas the activity of type II kinase increases as a function of time in G1 to a maximum at the G1/S border. In contrast, in the presence of dibutyryl-cyclic AMP, there is a decrease of type II kinase and a several-fold increase of type I kinase. In proliferating cells, the ratio of type I to type II was 0.37, while in the dibutyryl-cyclic AMP growth-arrested cells it was 3.96. The increase in type II kinase during G1 transition and the increase in type I kinase during dibutyryl-cyclic AMP treatment were dependent on protein synthesis. A similar pattern of type I and type II kinase expression during cell cycle progression occurred in Rat-1 fibroblasts and Rat-1 cells transformed by Rous sarcoma virus. The inclusion of dibuityryl-cyclic AMP in the growth media promoted a marked increase in type I holoenzyme, which was inhibited by cycloheximide, and a decrease in type II kinase. Neither AMP nor sodium butyrate had any effect on cellular kinase levels, whereas 8-bromo-cyclic AMP mimicked the action of dibutyryl-cyclic AMP. Estimation of half-lives for the kinase types showed that there was little turnover of either type during normal G1 progression, rapid turnover of both types as cells exited from mitosis, and selective turnover of type II upon addition of dibutyryl-cyclic AMP.
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PMID:Differential expression of type I and type II cyclic AMP-dependent protein kinases during cell cycle and cyclic AMP-induced growth arrest. 615 48

Incubation of C6 glioma cells with isoproterenol elicits an increase in cyclic AMP content, followed by an activation of cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). The cytoplasm of these glioma cells contains type II protein kinase and a small amount of cyclic AMP-independent protein kinase. Following the persistent activation of cyclic AMP-dependent protein kinase, catalytic subunits of this enzyme redistribute into particulate fractions. A maximal increase in nuclear protein kinase activity occurrs 45 to 60 min following isoproterenol. The addition of cyclic AMP or of Ca2+ with or without the specific ionophore A-23187 fails to increase the protein kinase activity of nuclei from control or isoproterenol-treated cells. Preincubation of the cells with vinblastine blocks the increase of nuclear protein kinase activity due to isoproterenol. If the incubation with vinblastine occurs simultaneously with isoproterenol, vinblastine fails to reduce the increase in nuclear protein kinase activity elicited by isoproterenol.
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PMID:Protein kinase translocation following beta-adrenergic receptor activation in C6 glioma cells. 624 1

Sarcomplasmic reticulum from rabbit fast skeletal muscle contains intrinsic protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) and a substrate. The protein kinase activity was Mg2+ dependent and could also phosphorylate exogenous protein substrates. Autophosphorylation of sarcoplasmic reticulum vesicles was not stimulated by cyclic AMP, neither was it inhibited by the heat-stable protein kinase inhibitor protein. The phosphorylated membranes had the characteristics of a protein with a phosphoester bond. An average of 73 pmol Pi/mg protein were incorporated in 10 min at 30 degrees C. Addition of exogenous cyclic AMP-dependent protein kinase increased the endogenous level of phosphorylation by 25-100%. Sarcoplasmic reticulum membrane phosphorylation, mediated by either endogenous cyclic AMP-independent or exogenous cyclic AMP-dependent protein kinase, occurred on a 100 000 dalton protein and both enzyme activities resulted in enhanced calcium uptake and Ca2+-dependent ATPase (ATP phosphohydrolase, EC 3.6.1.3), in a manner similar to cardiac microsomal preparations. Regulation of Ca2+ transport in skeletal sarcoplasmic reticulum may be mediated by phosphorylation of a 100 000 dalton component of these membranes.
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PMID:Phosphorylation of a 100 000 dalton component and its relationship to calcium transport in sarcoplasmic reticulum from rabbit skeletal muscle. 624 11

In Y1 adrenocortical tumor cells, corticotropin (ACTH), cyclic AMP, and 8-bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated ornithine decarboxylase activity (L-ornithine carboxy-lyase, EC 4.1.1.17) and steroidogenesis. The concentrations required for half-maximal activation of ornithine decarboxylase were 60 pM for ACTH and 1 mM for 8BrcAMP; the concentrations required for half-maximal activation of steroidogenesis were 50 pM for ACTH and 0.2 mM for 8BrcAMP. Ornithine decarboxylase activity increased 1.5 hr after the addition of these agents, reached a maximum between 4 and 6 hr, and then declined. Mutant clones with impaired ACTH-responsive adenylate cyclase systems [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]did not respond to ACTH with increased ornithine decarboxylase activity, but they responded normally to added cyclic AMP. These results indicate that adenylate cyclase and cyclic AMP are necessary for the stimulation of ornithine decarboxylase activity by ACTH. In a series of Y1(Kin) mutants with altered cyclic AMP-dependent protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37), the effects of ACTH on ornithine decarboxylase also were attenuated. These findings suggest that cyclic AMP-dependent protein kinase also plays a necessary role in the stimulation of ornithine decarboxylase activity by ACTH. The effects of ACTH on ornithine decarboxylase in the Kin mutants, however, were quantitatively different from the effects on steroidogenesis and did not closely reflect the degree of defect in cyclic AMP-dependent protein kinase activity. These differences suggest that the pathways of ACTH action leading to stimulation of steroidogenesis and ornithine decarboxylase activity diverge subsequent to activation of the protein kinase.
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PMID:Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase. 624 65

A membranal proteinase from brush-border epithelial cells of the rat small intestine was shown to bring about a restricted and limited degradation of the free catalytic subunit (C) of cyclic AMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) with concomitant inactivation of the kinase. This membranal proteinase exhibits a remarkable specificity. (i) It degrades C in its native conformation, but not after it has been heat-denatured. (ii) The degradation of C (Mr 40,000) does not proceed further, once a distinct clipped product (Mr 34,000) is formed. (iii) The undissociated ("stored") form of the enzyme (R2C2) is not attacked by the membranal proteinase, preserving both its potential catalytic activity and its molecular integrity. Only upon addition of cyclic AMP to release free C does the proteinase attack it. (iv) The membranal proteinase does not degrade the regulatory subunit (R), released by cyclic AMP from R2C2, although R is quite susceptible to degradation by other proteolytic enzymes. None of these features of the membranal proteinase could be reproduced with trypsin, chymotrypsin, clostripain, or papain. The specific, restricted, and limited action of this membranal enzyme raises the possibility that it may have a distinct physiological assignment associated with the bioregulation of cyclic AMP-dependent protein kinase.
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PMID:Degradative inactivation of cyclic AMP-dependent protein kinase by a membranal proteinase is restricted to the free catalytic subunit in its native conformation. 626 95


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