Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CD46 downregulation by measles virus (MV) occurs after expression of virus haemagglutinin (H) protein on the surface of the infected cell and is a consequence of CD46-H interaction on the cell membrane. To assess whether CD46 downregulation also occurs after CD46-H interaction when these two molecules are expressed on distinct cells, we used human T cell line Jurkat (expressing CD46) and transfected murine fibroblast line L stably expressing MV-H protein (L.H). FACS analysis shows that cell-to-cell contact of 1 h at 37 degrees C triggers a reduction of CD46 cell surface labelling as detected by MCI20.6, GB24 and J4-48 monoclonal antibodies. This reduction is similar to that observed after MV infection or after infection with recombinant vaccinia virus encoding MV-H protein. By contrast, MV-H protein was downregulated only when CD46-H interaction occurred on the same cell membrane. CD46 downregulation is specific for CD46-H interaction because it was not observed after coincubation of Jurkat cells with either L cells expressing MV nucleoprotein (L.NP) or L cells. Moreover, this downregulation could be blocked by either anti-CD46 or anti-H antibodies. The H-mediated CD46 downregulation is reversible and restricted to CD46 since expression of other surface markers (CD3, CD14, CD47 and CD63) is unaffected. It is apparently not mediated in a protein kinase (PK) A- or PKC-dependent manner. Altogether, our results provide an unequivocal demonstration that interaction between the extracellular domains of CD46 and MV-H is sufficient to trigger CD46 downregulation.
J Gen Virol 1995 Nov
PMID:Cell-to-cell contact via measles virus haemagglutinin-CD46 interaction triggers CD46 downregulation. 759 86

Lithium remains the most widely used treatment for bipolar disorder, and this monovalent cation represents one of psychiatry's most important treatments. Despite its demonstrated efficacy in reducing both the frequency and severity of recurrent affective episodes and decades of clinical use, the molecular mechanisms underlying its therapeutic actions have not fully been elucidated. In this report, we review the exciting recent progress in the identification of key components of signal transduction pathways (in particular, guanine nucleotide-binding proteins [G proteins], adenylyl cyclases, and protein kinase C isozymes) as targets for lithium's actions and attempt to integrate these effects with the large body of data emphasizing alterations in various neurotransmitter (particularly monoaminergic) systems. Regulation of signal transduction within critical regions of the brain by lithium affects the function of multiple neurotransmitter systems and may thus explain lithium's efficacy in protecting susceptible individuals from spontaneous, stress-induced, and drug-induced cyclic affective episodes. Recent evidence has also demonstrated significant effects of lithium on the regulation of gene expression in the central nervous system, effects that may play a major role in the long-term stabilization of mood. The identification of these intracellular targets for lithium's actions offers the potential for the development of novel, improved therapeutic agents and, in conjunction with molecular genetic approaches, may facilitate our understanding of the biological factors predisposing individuals to manic-depressive illness.
Arch Gen Psychiatry 1995 Jul
PMID:Signal transduction pathways. Molecular targets for lithium's actions. 759 29

1. Aromatic L-amino acid decarboxylase is the enzyme responsible for the decarboxylation step in both the catecholamine and the indolamine synthetic pathways. Immunological and molecular biological studies suggest that it is a single enzyme with one catalytic site but with different locations for attachment of the substrates. The enzyme is widely distributed in the brain and in peripheral tissues. 2. Recent investigations have shown that the enzyme is regulated by short term mechanisms that may involve activation of adenyl cyclase or protein kinase C. In addition, a long-term mechanism of activation by altered gene expression has also been suggested.
Gen Pharmacol 1995 Jul
PMID:Aromatic L-amino acid decarboxylase: biological characterization and functional role. 763 43

1. Incubation of bovine cerebral vessels (previously exposed to [3H]-noradrenaline) with nicotine for 30 sec produced a facilitation of the electrically-induced noradrenaline release, which was antagonized by hexamethonium, a blocker of nicotinic receptors. This facilitation was not observed when the incubation time was increased to 20 or 75 min. 2. Rauwolscine, an alpha 2-adrenoceptor blocker, enhanced and phorbol 12, 13-dibutyrate reduced the facilitator effect produced by 30 sec exposure to nicotine. 3. These data suggest: (1) presynaptic nicotinic receptors produce a facilitation of stimulated noradrenaline release; these receptors are easily desensitized by increasing the incubation time with nicotine; (2) protein kinase C and alpha 2-adrenoceptors appear to be involved in this process.
Gen Pharmacol 1995 Jul
PMID:Involvement of alpha 2-adrenoceptors and protein kinase C on nicotine-induced facilitation of noradrenaline release in bovine cerebral arteries. 763 58

Invertebrate photoreceptors use the inositol-lipid signaling cascade for phototransduction. A useful approach to dissect this pathway and its regulation has been provided by the isolation of Drosophila visual mutants. We measured extracellular changes of Ca2+ [delta Ca2+]o in Drosophila retina using Ca(2+)-selective microelectrodes in both the transient receptor potential (trp) mutant, in which the calcium permeability of the light-sensitive channels is greatly diminished and in the inactivation-but-no-afterpotential C (inaC) mutant which lacks photoreceptor-specific protein kinase C (PKC). Illumination induced a decrease in extracellular [Ca2+] with kinetics and magnitude that changed with light intensity. Compared to wild-type, the light-induced decrease in [Ca2+]o (the Ca2+ signal) was diminished in trp but significantly enhanced in inaC. The enhanced Ca2+ signal was diminished in the double mutant inaC;trp indicating that the effect of the trp mutation overrides the enhancement observed in the absence of eye-PKC. We suggest that the decrease in [Ca2+]o reflects light-induced Ca2+ influx into the photoreceptors and that the trp mutation blocks a large fraction of this Ca2+ influx, while the absence of eye specific PKC leads to enhancement of light-induced Ca2+ influx. This suggestion was supported by Ca2+ measurements in isolated ommatidia loaded with the fluorescent Ca2+ indicator, Ca Green-5N, which indicated an approximately threefold larger light-induced increase in cellular Ca2+ in inaC relative to WT. Our observations are consistent with the hypothesis that TRP is a light activated Ca2+ channel and that the increased Ca2+ influx observed in the absence of PKC is mediated mainly via the TRP channel.
J Gen Physiol 1994 Dec
PMID:Genetic dissection of light-induced Ca2+ influx into Drosophila photoreceptors. 769 63

1. The signal transduction process mediated by cyclic AMP that leads to the characteristic positive inotropic effect (PIE) in association with a positive lusitropic effect (acceleration of rate of twitch relaxation) has been well established. Relationships between accumulation of cyclic AMP, changes in intracellular Ca2+ transients and the PIE differ, however, depending on the mechanism of particular drugs that affect different steps in the metabolism of cyclic AMP. Selective partial agonists of beta 1-adrenoceptors and inhibitors of phosphodiesterase (PDE) III cause the accumulation of less cyclic AMP for a given PIE than does isoproterenol. In addition, in aequorin-microinjected canine ventricular muscle, selective inhibitors of PDE III, OPC 18790 and Org 9731, produced smaller decreases in the responsiveness of myofilaments to Ca2+ ions than isoproterenol, while a partial agonist of beta 1-adrenoceptors, denopamine, elicits a decrease in Ca2+ responsiveness of the same extent as does isoproterenol. 2. Activation of myocardial alpha 1-adrenoceptors, as well as stimulation of receptors for endothelin and angiotensin II, which accelerates hydrolysis of phosphoinositide (PI) to result in production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) are associated with very similar inotropic regulation: (1) the dependence on the species of animals of induction of the PIE; (2) an excellent correlation between the extent of acceleration of hydrolysis of PI and the PIE; (3) isometric contraction curves associated with a negative lusitropic effect; (4) the PIE associated with increases in myofibrillar responsiveness to Ca2+ ions; and (5) the selective inhibition of the PIE by an activator of protein kinase C (PKC), phorbol 12,13-dibutyrate (PDBu), with little effect on the PIE of isoproterenol and Bay k 8644. 3. A novel class of cardiotonic agents, namely, Ca2+ sensitizers such as EMD 53998 and Org 30029, act on the Ca(2+)-binding site of troponin C, increasing the affinity of these sites for Ca2+ ions, or at the actin-myosin interface to facilitate the cycling of cross-bridges. These agents produce a PIE with little change or decrease in Ca2+ transients and may bring about a significant breakthrough in the development of drugs for reversal of myocardial failure in the treatment of congestive heart failure.
Gen Pharmacol 1995 Jan
PMID:The effects of various drugs on the myocardial inotropic response. 771 48

1. The effects of a protein-tyrosine kinase inhibitor, genistein, and a protein-tyrosine phosphatase inhibitor, orthovanadate, were tested on the Ca(2+)-free contraction of the estrogen-dominated rat, which has been proved to be induced mainly via protein kinase C entirely independently of Ca2+. 2. Genistein (30 microM) significantly inhibited the contraction indicating participation of tyrosine kinase activity in the contraction. 3. Orthovanadate caused contraction concentration-dependently and augmented the Ca(2+)-free contraction at concentrations of more than 1 microM. The contraction by orthovanadate was not inhibited so significantly by genistein (30 microM). 4. Possible participation of tyrosine kinase activity in Ca(2+)-free contraction is discussed in addition to the formerly reported participation of protein kinase C.
Gen Pharmacol 1994 Dec
PMID:Effects of tyrosine kinase inhibitor, genistein, and phosphotyrosine-phosphatase inhibitor, orthovanadate, on Ca(2+)-free contraction of uterine smooth muscle of the rat. 772 Oct 45

The induction of macrophage procoagulant activity (PCA) has been shown to correlate with the development of fulminant hepatic necrosis after infection with murine hepatitis virus strain 3 (MHV-3). However, comparatively little is known about the early events in cells after viral infection leading to PCA expression. Accordingly, we investigated the early cellular events in the induction of macrophage PCA by MHV-3. MHV-3 stimulation of macrophages did not result in a detectable increase in intracellular calcium levels nor did stimulation of macrophages by calcium ionophores result in induction of PCA, suggesting that calcium transients were neither necessary nor sufficient for induction of PCA by MHV-3. Treatment of cells with phorbol myristate acetate had no effect on PCA induction; however, inhibition of protein kinase C (PKC) by staurosporine or H7 resulted in attenuation of macrophage PCA following MHV-3 stimulation (P < 0.05 compared with untreated macrophages), suggesting that although activation of PKC alone is insufficient for PCA induction, PKC may be an integral component of PCA induction by MHV-3. We have previously demonstrated that dimethyl prostaglandin E2 inhibited induction of PCA by MHV-3. In this study, treatment of cells by agents that increase intracellular cAMP (forskolin, isobutylmethyl xanthine) significantly inhibited PCA induction (P < 0.02). These results demonstrate that induction of macrophage PCA by MHV-3 involves PKC, but proceeds independently of changes in intracellular calcium, and that PCA expression is down-regulated by increases in intracellular cAMP.
J Gen Virol 1995 May
PMID:Effect of alterations in early signal transduction events on the induction of procoagulant activity by murine hepatitis virus strain 3 in vitro. 773 Aug 2

Mechanisms of Ca2+ sensitization of both myosin light chain (MLC) phosphorylation and force development by protein kinase C (PKC) were studied in permeabilized tonic smooth muscle obtained from the rabbit femoral artery. For comparison, the Ca2+ sensitizing effect of guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S) was examined, which had been previously shown to inhibit MLC phosphatase in phasic vascular smooth muscle. We now report that PKC activators (phorbol esters, short chain synthetic diacylglycerols and a diacylglycerol kinase inhibitor) and GTP gamma S significantly increase both MLC phosphorylation and force development at constant [Ca2+]. Major phosphorylation site occurring in the presence of phorbol-12,13-dibutyrate (PDBu) or GTP gamma S at constant [Ca2+] is the same serine residue (Ser-19) as that phosphorylated by MLC kinase in response to increased Ca2+ concentrations. In an ATP- and Ca(2+)-free solution containing 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), to avoid the kinase activity, both PDBu and GTP gamma S significantly decreased the rate of MLC dephosphorylation to half its control value. However, PDBu inhibited the relaxation rate more than did GTP gamma S. In the presence of microcystin-LR to inhibit the phosphatase activity, neither PDBu nor GTP gamma S affected MLC phosphorylation and force development. These results indicate that PKC, like activation of GTP binding protein, increases Ca2+ sensitivity of both MLC phosphorylation and force production through inhibition of MLC phosphatase.
J Gen Physiol 1994 Aug
PMID:A novel mechanism for the Ca(2+)-sensitizing effect of protein kinase C on vascular smooth muscle: inhibition of myosin light chain phosphatase. 780 49

Age-related alterations in binding sites of major second messengers and a selective adenosine 3',5'-cyclic monophosphate (cyclic-AMP) phosphodiesterase (PDE) in the gerbil brain were analysed by receptor autoradiography. [3H]Phorbol 12,13-dibutyrate (PDBu), [3H]inositol 1,4,5-trisphosphate (IP3), [3H]forskolin, [3H]cyclic-AMP, and [3H]rolipram were used to label protein kinase C (PKC), IP3 receptor, adenylate cyclase, cyclic-AMP dependent protein kinase (PKA), and Ca2+/calmodulin-independent cyclic-AMP PDE, respectively. In middle-aged gerbils (16 months old), [3H]PDBu binding was significantly reduced in the hippocampal CA1 sector, thalamus, substantia nigra, and cerebellum, compared with young animals (1 month old). [3H]IP3 binding revealed significant elevations in the nucleus accumbens, hippocampal CA1 sector, dentate gyrus, and a significant reduction in cerebellum of middle-aged gerbils. [3H]Forskolin binding in middle-aged animals was significantly increased in the nucleus accumbens and hilus of dentate gyrus, but was diminished in the substantia nigra and cerebellum. On the other hand, in middle-aged animals, [3H]cyclic-AMP binding revealed a significant elevation only in the hippocampal CA3 sector, whereas [3H]rolipram binding showed a significant reduction in the thalamus and cerebellum. Thus, the age-related alteration in these binding sites showed different patterns among various brain regions in middle-aged gerbils indicating that the binding sites of PKC, IP3, and adenylate cyclase are more markedly affected by aging than those of PKA and cyclic-AMP PDE and that the hippocampus and cerebellum are more susceptible to these aging processes than other brain regions. The findings suggest that intracellular signal transduction is affected at an early stage of senescence and this may lead to neurological deficits.
J Neural Transm Gen Sect 1994
PMID:Age-dependent changes in second messenger and rolipram receptor systems in the gerbil brain. 787 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>