Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipocortin I (LPC-I, also called annexin I) is a 35-kD protein that binds phospholipids and actin in a Ca(++)-dependent manner. It is also a major substrate for EGF receptor/kinase and protein kinase C, and a putative inhibitor of phospholipase A2, which produces chemical mediators to cause inflammation. Psoriasis (PS) is an inflammatory skin disease characterized by a rapid turnover of keratinocytes and a defect in keratinization with increased activities of phospholipase C and A2, and EGF receptor. To understand the mechanism of the PS lesion formation and the function of LPC-I, its distribution was studied in the epidermis of PS, subacute eczema and normal skin, and in tumor cells of seborrheic keratosis and Bowen's disease. This study involved immunofluorescence and immunoblotting using affinity-purified polyclonal and monoclonal antibodies specific to LPC-I and to its Ca(++)-bound form. In normal, nonlesional PS and subacute eczema epidermis, LPC-I was detected mainly in the cytoplasm of the suprabasal cells, although it was on the inner aspects of the plasma membrane in some parts of the granular layer. In lesional epidermis of PS, it was localized mainly on the inner aspects of the plasma membrane, but not in the cytoplasm of the whole suprabasal cells as the Ca(++)-bound form, indicating a preferential localization on the plasma membrane. This membrane-binding of LPC-I was also observed in seborrheic keratosis, but not in Bowen's disease. These results suggest that the binding of LPC-I to the plasma membrane occurs actually in living cells, plays a role, not necessarily disease specific, in the PS lesion formation, and has some relevance to normal or abnormal differentiation of keratinocytes.
 ...
PMID:Lipocortin I (annexin I) is preferentially localized on the plasma membrane in keratinocytes of psoriatic lesional epidermis as shown by immunofluorescence microscopy. 183 17

Prostaglandin E2 (PGE2, 5 ng/ml to 5 micrograms/ml) induced a dose-dependent increase in cAMP accumulation, inositol phosphates (IPs) accumulation, and cytoplasmic free Ca2+ ([Ca2+]i) in a clonal osteoblast-like cell line, MOB 3-4. In contrast, prostaglandin F2 alpha (PGF2 alpha, 5 ng/ml to 5 micrograms/ml) stimulated increases in IPs accumulation and [Ca2+]i without stimulating an increase in cAMP accumulation. Both PGE2 (greater than 0.5 micrograms/ml) and PGF2 alpha (greater than or equal to 5 micrograms/ml) increased cytoplasmic pH (pHi) from approximately 7.15 to 7.35 in BCECF-loaded cells. A tumor promotor, phorbol 12-myristate 13-acetate (PMA, 0.1-100 nM) also increased pHi without effect on phosphoinositide hydrolysis. Both PGE2-(5 micrograms/ml) and PMA- (100 nM) induced cytoplasmic alkalinization was inhibited by removal of extracellular Na+, or by pretreatment of the cells with amiloride (0.5 mM), an inhibitor of Na+/H+ exchange, or H-7 (100 microM), a nonspecific inhibitor of protein kinase C. Thus, MOB 3-4 cells appeared to possess PGE2 receptors and PGF2 alpha receptors: the former are coupled to adenylate cyclase and phospholipase C, and the latter are predominantly coupled to phospholipase C. Also the cells appeared to possess an amiloride-sensitive Na+/H+ exchange activity, which increases pHi in response to PGE2 and PGF2 alpha, as well as to PMA. Long-term (48 hr) exposure of the cells to PGE2 at a high concentration (5 micrograms/ml), but not to PGF2 alpha and PMA, decreased DNA synthesis in the serum-deficient medium. Thus, cytoplasmic alkalinization appeared insufficient for cell replication. At least in MOB 3-4 cells, the inhibitory effect of PGE2 on DNA synthesis may be due to the cAMP messenger system.
 ...
PMID:Effects of prostaglandin E2 and F2 alpha on cytoplasmic pH in a clonal osteoblast-like cell line, MOB 3-4. 184 35

Phospholipase C was purified from human melanoma grown as solid tumors in nude mice. The specific activity of the pure enzyme was approx. 100 mumol/min per mg; its apparent molecular mass was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis to be 150 kDa. The enzyme required calcium for activity and was activated by deoxycholate in the presence of the substrate phosphatidylinositol. The melanoma phospholipase C has a distinctly different substrate preference than those identified from normal tissues; it prefers phosphatidylinositol to phosphatidylinositol bisphosphate. The tumor enzyme was approx. 4-5-fold more active using phosphatidylinositol than phosphatidylinositol bisphosphate as the substrate.
 ...
PMID:Phospholipase C from human melanoma: purification and characterization of a phosphatidylinositol-selective enzyme. 184 29

Carcinoembryonic antigen (CEA) was highly effectively extracted with phosphatidylinositol-specific phospholipase C (PI-PLC) from various source materials. The yield of CEA was, in some cases, 20-30 times more than that obtained by the usual method with perchloric acid. Addition of 0.1-0.2 units of PI-PLC to 1 g tumor tissue and incubation at 37 degrees C for 1 h with continuous shaking seem to be practically sufficient for CEA extraction. A simple purification procedure for CEA after extraction with PI-PLC is proposed. The immunochemical properties of CEA thus obtained were found to be identical to those of CEA obtained by the usual method.
Tumour Biol 1991
PMID:Highly effective extraction of carcinoembryonic antigen with phosphatidylinositol-specific phospholipase C. 185 20

CEA as well as normal cross-reacting antigens (NCA) are fixed to the cell membrane via phosphatidylinositol (PI). To find out whether these antigens are internalized after antibody contact, acid pH desorption was compared to phospholipase C (PLC)-mediated cleavage of the antigen anchor. With the former procedure, marked differences in the desorbability of individual MAbs were noted, while PLC was able to cleave off surface-bound immune complexes irrespective of the MAb involved. From this it is concluded that internalization of MAb complexes of CEA/NCA, if occurring at all, is a low efficiency process.
Tumour Biol 1991
PMID:Detachment of cell surface-bound anticarcinoembryonic antigen immune complexes by phospholipase C. 196 49

The molecular nature and possible presence of a glycan-phosphatidylinositol anchor (GPI-anchor) in CA125 molecules was investigated. Serial lectin affinity chromatography and N- or O-glycanase treatment to reduce antigenicity showed that CA125 contained certain N- and O-glycosylated sugar chains in the molecule, like a glycoprotein. CA125 released from ovarian cancer tissues increased time-dependently following phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, concomitant with the release of tissue-unspecific alkaline phosphatase. Western blotting of CA125 treated by PI-PLC showed a single band of 90 kD instead of the 162- and 76-kD bands of the native antigen. Further, ovarian cancer tissues subjected to PI-PLC treatment lost the immunohistochemical localization of CA125 with OC125 antibody. Consequently, it is strongly suggested that CA125 is a glycoprotein that has both N- and O-linked sugar chains and a membranous GPI-anchoring moiety, and further, that its 90-kD form is the antigen without the GPI-anchor.
Tumour Biol 1991
PMID:Molecular nature and possible presence of a membranous glycan-phosphatidylinositol anchor of CA125 antigen. 196 50

Vascular permeability factor (VPF), a tumor-secreted heparin-binding protein (Mr approximately 38,000), is responsible for increased vessel permeability and fluid accumulation associated with tumor growth. Vascular permeability factor also promotes the growth of human umbilical vein endothelial cells (EC) and bovine pulmonary ECs in vitro. It is shown for the first time that guinea pig VPF (half-maximal and maximal dose approximately 0.4 and 22 pmol/l (picomolar), respectively), as well as human VPF, are potent stimuli for human ECs resulting in [Ca2+]i increases (maximal three- to fourfold) and inositol triphosphate (IP3) formation. Unlike the maximal responses to thrombin and histamine, the [Ca2+]i response to a maximal VPF dose was preceded by a characteristic 10- to 15-second delay. Guinea pig VPF also selectively increased [Ca2+]i in cultured aortic and pulmonary artery ECs, but not aortic smooth muscle cells, human fibroblasts, or neutrophils. Affinity-purified rabbit antibody (raised to a synthetic peptide representing VPF N-terminal amino acids 1 to 24) adsorbed all vessel permeability-increasing activity, EC growth-promoting activity, and specifically all activity responsible for increasing EC [Ca2+]i. Similar to other mediators that increase [Ca2+]i in cultured ECs, VPF also induced a 200% increase in von Willebrand factor release. Together these data indicate that VPF acts directly on ECs and that rapid cellular events in its in vivo/in vitro actions are likely to involve phospholipase C activation, [Ca2+]i increase, and von Willebrand factor release.
 ...
PMID:Tumor-secreted vascular permeability factor increases cytosolic Ca2+ and von Willebrand factor release in human endothelial cells. 198 67

The tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) can enhance or inhibit lymphocyte proliferation. Enhancement correlated with increased interleukin 2 (IL-2) production and activation of protein kinase C while inhibition correlated with decreased IL-2 and downregulation of protein kinase C activity (D.S. Grove and A.M. Mastro, Cancer Res. 51, 82-88). In this study, various activators and inhibitors of protein kinase C were used in order to try to separate the effects of TPA on this enzyme from its effects on IL-2 production and determine if protein kinase C activity was directly or indirectly related to IL-2 production. 1,2-Dioctanoylglycerol, 1-oleoyl-2-acetyl-glycerol, phospholipase C, and two "rationally designed" activators, 6-(N-decylamino)-4-hydroxy-methylindole and 3-(N-acetylamino)-5-(N-decyl-N-methylamino)-benzyl alcohol, were tested. Some activators enhanced proliferation in the presence of a Ca2+ ionophore, ionomycin, but not concanavalin A. Some activators suppressed proliferation and downregulated protein kinase C. Others neither downregulated protein kinase C nor inhibited IL-2 production and proliferation. However, inhibition or downregulation of protein kinase C activity always correlated with decreased IL-2 and depressed proliferation. Thus, the evidence in this and the previous study suggests that activation of protein kinase C is directly related to IL-2 production in activated T cells.
 ...
PMID:Differential activation and inhibition of lymphocyte proliferation by modulators of protein kinase C: diacylglycerols, "rationally designed" activators and inhibitors of protein kinase C. 199 92

An exciting new approach to the treatment of cancer is the development of therapeutic strategies which target growth factors and the signal transduction pathways elicited by them. The rationale for targeting the processes which regulate cell proliferation rests on the contention that the malignant phenotype is maintained as a result of alterations in the biochemistry of growth control. The challenge is to design novel anticancer agents which exploit qualitative or quantitative differences in the biochemical elements controlling tumour cell growth and thereby achieve tumour selectivity. A wide variety of drugs are currently under development and include agents which block growth factor-receptor interaction, or which inhibit the action or formation of second messengers such as protein kinase C or phospholipase C. Although in its infancy, the use of inhibitors of growth factor action as antineoplastic agents has already proven effective against some tumours.
Tumour Biol 1991
PMID:Mitogenesis and the search for new targets for anticancer drug design. 199 1

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulates a rapid increase in ornithine decarboxylase (EC 4.1.1.17; ODC) activity in target cells. Here we demonstrate that this process involves a rapid accumulation of ODC mRNA, which is maximal 3 h after treatment (three- to eightfold greater than control cells) and decays to control levels within 18 h. Stimulation of ODC mRNA by TPA is blocked by phorbol dibutyrate down-regulation of protein kinase C (PKC). ODC mRNA was also induced by the PKC activators, phospholipase C and 1-oleoyl-2-acetyl-rac-glycerol, and blocked by kinase inhibitors (trifluoroperazine, H7, and palmitoyl-L-carnitine), consistent with a requirement for PKC activation in the induction mechanism. However, the non-PKC-specific protein kinase inhibitor HA1004 also suppressed expression of ODC mRNA in response to TPA, under conditions where it did not inhibit PKC, suggesting that additional kinases may be involved in the intracellular signalling process. The stability of the ODC mRNA (control value = 6.2 +/- 1.6 h) is not significantly changed by either TPA (5.7 +/- 0.8 h) or by cycloheximide (6.0 h). These results are inconsistent with any contribution from altered mRNA half-life towards the accumulation of ODC mRNA following treatment with phorbol ester tumor promoters.
 ...
PMID:Involvement of protein kinase C in the regulation of ornithine decarboxylase mRNA by phorbol esters in rat hepatoma cells. 201 52


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