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:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have demonstrated enhanced phosphorylation of phospholipase C-tau (PLC-tau), a key regulatory enzyme in phosphoinositide metabolism, in cells treated with platelet-derived growth factor (PDGF) and epidermal growth factor, both of which act via specific receptor tyrosine kinases. Our studies on BALB/c-3T3 cells show that agents that promote cellular cyclic AMP accumulation also increase the phosphorylation, specifically the serine phosphorylation, of this enzyme. Increased phosphorylation of PLC-t (2-3-fold) was evident within 5-10 min of addition of isobutylmethylxanthine (IBMX) and either cholera toxin or forskolin to cells, and persisted for at least 3 h. Treatment of cells with cyclic AMP agonists also enhanced, with similar kinetics, the phosphorylation of a 76 kDa protein co-precipitated by anti-PLC-tau monoclonal antibodies. Brief exposure of cells to cholera toxin/IBMX or forskolin/IBMX decreased inositol phosphate formation induced by the GTP-binding protein (G-protein) activator aluminium fluoride by approx. 50%, but was without effect on PDGF-stimulated inositol phosphate formation. These findings suggest that PLC-tau, and perhaps the 76 kDa co-precipitated protein, are substrates of cyclic AMP-dependent protein kinase in BALB/c-3T3 cells: however, the lack of effect of cyclic AMP elevation on PDGF-stimulated inositol phosphate formation indicates that the intrinsic activity of PLC-tau is unaltered by cyclic AMP-mediated phosphorylation.
...
PMID:Cyclic AMP agonists induce the phosphorylation of phospholipase C-tau and of a 76 kDa protein co-precipitated by anti-(phospholipase C-tau) monoclonal antibodies in BALB/c-3T3 cells. Relationship to inositol phosphate formation. 170 22

PC12 cells contain at least three immunologically distinct phospholipase C (PLC) isozymes, PLC-beta, PLC-gamma, and PLC-delta. Treatment of PC12 cells with nerve growth factor (NGF) leads to an increase in the phosphorylation of PLC-gamma, but not of PLC-beta or PLC-delta. This increase can be seen in as little as 1 minute. The increased phosphorylation occurs on both serine and tyrosine residues, with the major increase being in the former. This result suggests the possibility that the NGF-dependent increase in phosphoinositide hydrolysis in PC12 cells is due to selective phosphorylation of PLC-gamma by serine and tyrosine protein kinases associated with the NGF receptor.
...
PMID:Nerve growth factor stimulates phosphorylation of phospholipase C-gamma in PC12 cells. 170 47

Cross-linking of the surface antigen receptor on B lymphocytes has been demonstrated to lead to activation of phospholipase C (PLC) with subsequent increases in production of inositol phosphates and diacylglycerol. In turn, these second messengers increase cytosolic free calcium [( Ca2+]i) and activate the serine threonine phosphotransferase protein kinase C (PKC). These processes are thought to play a major role in B cell activation and proliferation. However, the mechanism linking the B lymphocyte antigen receptor to phospholipase C remains to be identified. We demonstrate herein that activation of the antigen receptor on human lymphocytes, in addition to activation of PLC, increases tyrosine phosphorylation of specific substrates. Tyrphostins, a new class of tyrosine kinase inhibitors which compete for substrate binding site of specific tyrosine kinases have recently been synthesized. Preincubation of B lymphocytes with two different tyrphostins blocked anti-IgM-induced proliferation, oncogene expression, tyrosine phosphorylation, increases in [Ca2+]i, and production of inositol phosphates. The same inhibitors were without effect on B cell proliferation induced by phorbol esters and cation ionophores which directly activate PKC and increase [Ca2+]i thus bypassing PLC. These findings strongly indicate that tyrphostins do not exhibit significant nonspecific toxicity and suggest that they act proximal to PLC. The ability of the tyrphostins to block increases in [Ca2+]i and inositol phosphate production, after activation of the B cell antigen receptor, indicates that a tyrosine kinase acts as an essential link between the B cell antigen receptor and PLC.
...
PMID:Activation of phospholipase C in human B cells is dependent on tyrosine phosphorylation. 170 65

We have shown that platelets stimulated with thrombin or guanosine 5'-[gamma-thio]triphosphate (GTP[S]), both of which activate phospholipase C and protein kinase C (PKC), show enhancement of 3-phosphorylated phosphoinositide accumulation (3-PPI). We now report the following. (1) Inhibition of thrombin- or GTP[S]-stimulated PKC by pseudo-substrate peptide (RFARK) added to permeabilized platelets markedly inhibits 3-PPI, whereas the serine/threonine phosphatase inhibitor, okadaic acid, promotes 3-PPI. PKC activity, insufficient in itself for fully activating 3-PPI, appears crucial to receptor and post-receptor stimulation of 3-PPI, even when tyrosine phosphorylation is unimpaired. (2) Alteration of Gi by ADP-ribosylation only slightly affects the stimulation of 3-PPI by thrombin, and activation of the G-protein Gi by adrenaline has no effect on 3-PPI. (3) Inhibition of PKC blocks activated secretion of platelet-derived growth factor (PDGF). However, PDGF cannot promote platelet 3-PPI, and thus cannot account for the inhibitory effects of RFARK on 3-PPI.
...
PMID:Protein kinase C regulates the stimulated accumulation of 3-phosphorylated phosphoinositides in platelets. 171 81

The human T-cell line Jurkat was found to contain at least two immunologically distinct isoforms of inositol phospholipid-specific phospholipase C (PLC), PLC-beta 1 and PLC-gamma 1. Treatment of Jurkat cells with antibody to CD3 led to phosphorylation of PLC-gamma 1 but not of PLC-beta 1. The phosphorylation of PLC-gamma 1 occurred rapidly and transiently on both serine and tyrosine residues; tyrosine phosphorylation reached a maximum level less than 1 min after stimulation and decreased rapidly, both in the presence and in the absence of orthovanadate. Two-dimensional phosphopeptide map analysis revealed that the major sites of tyrosine and serine phosphorylation in PLC-gamma 1 from activated Jurkat cells are the same as those in PLC-gamma 1 from cells treated with peptide growth factors such as epidermal growth factor and platelet-derived growth factor. Previously, it has been shown that multiple phosphorylation of PLC-gamma 1 by the growth factor receptor tyrosine kinases leads to activation of PLC-gamma 1. Thus, the current data suggest that inositol phospholipid hydrolysis triggered by the T-cell antigen receptor-CD3 complex is due, at least in part, to activation of PLC-gamma 1 and that the mechanism by which this activation is achieved involves phosphorylation of multiple tyrosine residues on PLC-gamma 1 by a nonreceptor tyrosine kinase coupled to the T-cell antigen receptor-CD3 complex.
...
PMID:CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line. 182 97

Intracellular signalling pathways mediating the effects of growth factors and oncogenes on cell growth and transformation present a challenging new class of target sites for anticancer drug development. Several drugs are already available that may act in this way, including drugs that act on protein serine/threonine kinases, protein tyrosine kinases and phospholipase C, as well as inhibitors of myo-inositol signalling. As our understanding of the signalling pathways involved in growth control increases, new sites for pharmacological intervention will become apparent. Garth Powis reviews the evidence that this approach may eventually lead to new, more selective drugs for treating cancer.
...
PMID:Signalling targets for anticancer drug development. 186 34

The phenolic antioxidant 2,6-bis(1,1-dimethyl ethyl)-4-methylphenol (BHT) evokes a transient phosphorylation of two platelet proteins of Mr 20,000 and 47,000 that are well-known substrates of protein kinase C (PKC) and, similarly to phorbol esters, a slight but persistent phosphorylation of a protein of Mr 26,000. These effects are observed both in the presence and in the absence of extracellular calcium, but are abolished in the presence of the protein kinase C inhibitor staurosporine. The phosphorylation of the 47 kDa protein takes place mostly at the serine and, to a lesser extent, at threonine residues. BHT induces an increased binding of tritiated phorbol dibutyrate to platelets indicating a PKC translocation from cytosol to plasma membrane. Addition of BHT (20 microM) a few min prior to thrombin causes inhibition of both agonist-evoked protein phosphorylation and increase in the Ca2+ concentration, the latter inhibition being counteracted by staurosporine. The inhibitory effect lasts for several minutes even after removal of BHT from the cellular suspending medium. Similar results are obtained with nordihydroguaiaretic acid, whereas 2- and 3-tert-butyl-4-methoxyphenol (BHA) produce only slight effects. BHT activates the protein kinase C purified from pig brain in a concentration-dependent manner (up to 200 microM), whereas it does not affect the activity of other purified protein kinases such as type 1 and 2 casein kinases, type II A, II B and III tyrosine protein kinases from rat spleen and the catalytic subunit of cyclic AMP-dependent protein kinase. It is concluded that, similarly to diacylglycerols and phorbol esters, these phenolic antioxidants activate the protein kinase C, which in turn desensitizes platelets towards subsequent phospholipase C activation.
...
PMID:The antioxidant butylated hydroxytoluene stimulates platelet protein kinase C and inhibits subsequent protein phosphorylation induced by thrombin. 188 50

Human monocytes release arachidonic acid upon stimulation with a variety of soluble or particulate agents. These include: phorbol esters (i.e., 12-O-tetradecanoate phorbol-13-acetate, TPA), calcium ionophores (ionomycin), serum-treated zymosan (STZ) concanavalin A (Con A), and, to a minor degree, lipopolysaccharides (LPS). Protein Kinase C activation or increased intracellular Ca2+ are common features of the actions of most, if not all, of these stimuli. Prevention of PKC activation by the use of staurosporine or chelation of extracellular calcium by EGTA selectively impaired AA release, indicating that PLA2 may be regulated by either pathway concurrently. The generation of inositol phosphates and diacylglycerol by the action of phospholipase C, notably upon interaction with opsonized particles during phagocytosis, apparently constitutes the physiological correlate of stimulation via these agents. Release of arachidonic acid by the action of PLA2 or other phospholipid hydrolyzing enzymes leads directly to the formation of cyclooxygenase products. In the presence of markedly elevated calcium concentrations, 5-lipoxygenase (LO) is activated as well, leading to the formation and release of leukotrienes. Agents which stimulate AA release also initiate other monocyte functions, including generation of reactive oxygen intermediates and lymphokine release. This observation makes it tempting to implicate PLA2 activation in many aspects of monocyte physiology. However, no correlation with PLA2 activation and either superoxide or lymphokine release was found when multiple stimuli, including TPA, ionomycin, serum-treated zymosan, concanavalin A, or LPS, were compared simultaneously. Instead, our results indicate that PLA2 activation is regulated by the same mechanisms, including PKC activation and increased Ca2+, as are other enzymes which determine expression of monocyte function. Phospholipase A2 (PLA2) hydrolyzes fatty acid from the sn-2 position of a wide variety of phospholipids. Substrates for this (these) enzyme(s) include species which contain a variety of polar head groups (choline, serine, ethanolamine, etc.) and some phospholipids with either linkages in sn-1. In many cell types, including human monocytes, phospholipase A2 commonly acts on substrates containing arachidonic acid (AA). The liberation of free arachidonate is a first step in the metabolism of prostaglandins, hydroxyeicosatetraeinoic acids, (HETE'S), and leukotrienes (Lt's). Monocytes and macrophages have been shown to be rich sources of arachidonate and its metabolites. Some biologic properties of monocytes, notably their role as immunomodulating cells, have been attributed to eicosanoid production and release. Accordingly, much of the interest regarding PLA2 in human monocytes centers on this aspect of their function.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Functional consequences of phospholipase A2 activation in human monocytes. 196 68

Intracellular free [Ca2+]i was measured using fura-2 in synaptosomes prepared from cerebral cortices of adult male rats (12 weeks). L-(+)-Glutamate, D-(-)-glutamate, and quisqualate produced similar dose-dependent increases in [Ca2+]i, with EC50 values of 0.38 microM, 0.74 microM, and 0.1 microM, respectively, and maximum increases of approximately 40%. Ibotenate showed less affinity (EC50 4.4 microM) but had a greater maximum effect (57%). N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) did not increase [Ca2+]i. The increases in [Ca2+]i induced by quisqualate and ibotenate were not diminished in the absence of extrasynaptosomal Ca2+. L-2-Amino-4-phosphonobutyrate (L-AP4) (1 microM) completely blocked the changes in [Ca2+]i induced by L-(+)-glutamate, D-(-)-glutamate, quisqualate, or ibotenate. The effects of quisqualate and ibotenate on [Ca2+]i were also blocked by coincubation of synaptosomes with L-(+)-serine-O-phosphate (L-SP) (1 mM) (which, like L-AP4, blocks the effects of quisqualate and ibotenate on inositol phospholipid metabolism). 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX) had no effect on agonist-mediated increases in [Ca2+]i when coincubated with either quisqualate or ibotenate. These data are consistent with the existence of presynaptic glutamate receptors (of the excitatory amino acid metabotropic type) which activate phospholipase C leading to the elevation of inositol 1,4,5-trisphosphate and release of Ca2+ from intracellular stores.
...
PMID:Presynaptic glutamate/quisqualate receptors: effects on synaptosomal free calcium concentrations. 197 84

A component that causes contraction of the isolated guinea pig tracheal smooth muscle was isolated in homogeneous form from the venom of the pedicellaria of the sea urchin, Toxopneustes pileolus. It is named Contractin A. Contractin A has 18,000 Da with a total residue of 138 amino acids. The molecular weight is about 17,700. The N-terminal amino acid is serine. The partial amino acid sequence was determined up to 37 residues. Direct comparison of sea urchin Contractin A does not show any similarity in amino acid sequence to toxins isolated from other marine toxin producers such as sea snakes, sea anemones, or marine worms. Contractin A caused contraction of the tracheal smooth muscle in a dose-dependent manner. Furthermore, Contractin A relaxed the contraction induced by histamine. The contraction and relaxation activity of Contractin A on the tracheal smooth muscle is reduced by a cyclooxygenase inhibitor such as indomethacin. The contraction induced by Contractin A is also inhibited by a phospholipase C inhibitor but not by a phospholipase A2 inhibitor. These results suggest that in the isolated guinea pig tracheal smooth muscle, the response to Contractin A may be effected through activated phospholipase C.
...
PMID:Purification and characterization of Contractin A from the pedicellarial venom of sea urchin, Toxopneustes pileolus. 198 11


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

---