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)

Most mammalian cells have the capacity to migrate. When placed into culture, cells will generally display a set rate of basal, unstimulated locomotion. The cells will begin to move in one direction and, after some time, change directions resulting in a random walk. External stimuli can influence cell motility in several ways to either enhance or retard the rate of migration (chemokinesis), to change the average amount of cell migration observed before the cell turns (persistence), or to increase the directionality of movement by limiting the number of turns made by the cells. Several factors have been identified that stimulate cell movement, but the signaling mechanisms that mediate this induced cell movement have only recently begun to be studied. In this review, we discuss the signals that support the directional movement of fibroblasts and epithelial cells in response to chemoattractant gradients. The work will emphasize studies carried out by our laboratory and others on the stimulation of cell motility by the PDGF. These results indicate that at least two sets of signaling molecules cooperate to regulate cell motility in vivo. These include phospholipase C-gamma, phosphoinositide-3' kinase and the Ras-GTPase activating protein Ras-GAP. The first set are those which bind to the intracellular domain of the receptor tyrosine kinase and bring about the phosphorylation and/or activation of intracellular effectors proximal to the receptor. The second is a set of down-stream effectors that regulate either the rate of cell movement or the directionality of that movement depending on the cell type. These include Ras and the Ras-related GTPase Rac along with free phosphoinositides and calcium ions that regulate the actin polymerization machinery. Signals that mediate nuclear changes leading to cell proliferation, such as elements of the MAP kinase pathway, do not appear to play a role in PDGF-stimulated cell migration. Current work thus suggests that a coordinated spatial regulation of signaling elements that interact with the cell membrane and cytoskeleton but not necessarily with nuclear elements is the controlling mediator of directional cell motility.
...
PMID:Signaling mechanisms in growth factor-stimulated cell motility. 925 9

Engagement of the mast cell high-affinity receptor for immunoglobulin E (IgE), FcepsilonRI, induces tyrosine phosphorylation of Syk, a non-receptor tyrosine kinase, that has been demonstrated as critical for degranulation. Herein we describe a synthetic compound, ER-27319, as a potent and selective inhibitor of antigen or anti-IgE-mediated degranulation of rodent and human mast cells. ER-27319 affected neither Lyn kinase activity nor the antigen-induced phosphorylation of the FcepsilonRI but did effectively inhibit the tyrosine phosphorylation of Syk and thus its activity. As a consequence, tyrosine phosphorylation of phospholipase C-gamma1, generation of inositol phosphates, release of arachidonic acid, and secretion of histamine and tumor necrosis factor alpha were also inhibited. ER-27319 did not inhibit the anti-CD3-induced tyrosine phosphorylation of phospholipase C-gamma1 in Jurkat T cells, demonstrating a specificity for Syk-induced signals. In contrast the tyrosine phosphorylation and activation of Syk, induced by in vitro incubation with the phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) of FcepsilonRI gamma subunit or by antigen activation of RBL-2H3 cells, was specifically inhibited by ER-27319. However, when ER-27319 was added to immunoprecipitated Syk, derived from activated cells, no effect was seen on Syk activity. ER-27319 did not inhibit the tyrosine phosphorylation of Syk induced by activation in the presence of Igbeta ITAM or the anti-IgM-induced phosphorylation of Syk in human peripheral B cells. Therefore, ER-27319 selectively interferes with the FcepsilonRI gamma phospho-ITAM activation of Syk in vitro and in intact cells. These results confirm the importance of Syk in FcepsilonRI-mediated responses in mast cells and demonstrate the mast cell selectivity and therapeutic potential of ER-27319 in the treatment of allergic disease.
...
PMID:ER-27319, an acridone-related compound, inhibits release of antigen-induced allergic mediators from mast cells by selective inhibition of fcepsilon receptor I-mediated activation of Syk. 935 85

Lysophosphatidic acid (LPA) is a lipid mediator which acts on its putative G protein-coupled receptor (GPCR). Recently, activation of signal transducers and activators of transcription (STATs) mediated by GPCR has been reported. In this study, we examined the effect of LPA on STAT activation using the electrophoretic mobility shift assays and the heterologous promoter analysis in human epidermoid carcinoma A431 cells. We found that LPA inhibited epidermal growth factor (EGF)-induced Stat1 activation in a concentration-dependent manner. Other phospholipase C (PLC)-coupled GPCR agonists, bradykinin and ATP, also inhibited Stat1 activation. This inhibitory effect of LPA was completely mimicked by an activator of protein kinase C (PKC), a PLC-downstream effector. These findings suggest that the inhibitory effect on EGF-induced Stat1 activation may be a general characteristic of PLC-coupled GPCRs and PKC pathway may be mainly associated with this inhibitory effect. This is the first evidence showing that GPCR agonists inhibit the Janus kinase-independent Stat1 activation induced by receptor tyrosine kinase.
...
PMID:Lysophosphatidic acid inhibits epidermal-growth-factor-induced Stat1 signaling in human epidermoid carcinoma A431 cells. 939 58

A new family of neuronal survival factors comprised of glial cell line-derived neurotrophic factor (GDNF) and neurturin has recently been described (Kotzbauer, P. T., Lampe, P. A., Heuckeroth, R. O., Golden, J. P., Creedon, D. J., Johnson, E. M., Jr., and Milbrandt, J. (1997) Nature 384, 467-470). These molecules, which are related to transforming growth factor-beta, are important in embryogenesis and in the survival of distinct neuronal populations. These molecules signal through a novel receptor system that includes the Ret receptor tyrosine kinase, a ligand (i.e. GDNF or neurturin), and an accessory glycosyl-phosphatidylinositol-linked molecule that is responsible for high affinity binding of the ligand. Two accessory molecules denoted GDNF family receptor 1 and 2 (GFRalpha-1 and GFRalpha-2) have been described that function in GDNF and neurturin signaling complexes. We have identified a novel co-receptor belonging to this family based on similarity to GFRalpha-1, which we have named GFRalpha-3. GFRalpha-3 displays 33% amino acid identity with GFRalpha-1 and 36% identity with GFRalpha-2. Despite the similarity of GFRalpha-3 to GFRalpha-1 and GFRalpha-2, it is unable to activate Ret in conjunction with GDNF, suggesting that there are likely additional undiscovered ligands and/or Ret-like receptors to be identified. GFRalpha-3 is anchored to the cell membrane by a phosphatidylinositol-specific phospholipase C-resistant glycosyl-phosphatidylinositol linkage. GFRalpha-3 is highly expressed by embryonic day 11 but is not appreciably expressed in the adult mouse. In situ hybridization analyses demonstrate that GFRalpha-3 is located in dorsal root ganglia and the superior cervical sympathetic ganglion. Comparison of the expression patterns of GFRalpha-3 and Ret suggests that these molecules could form a receptor pair and interact with GDNF family members to play unique roles in development.
...
PMID:Identification and characterization of GFRalpha-3, a novel Co-receptor belonging to the glial cell line-derived neurotrophic receptor family. 945 75

The effects of omega 3 fatty acids and epidermal growth factor (EGF) on the activity of receptor tyrosine kinase (RTK) and phospholipase C (phosphatidylinositol (PI)-specific PLC) were examined in EMT6 cells. The non-omega 3 treated, non-EGF stimulated cells served as controls. Treatment of the EMT6 cells with omega 3 fatty acids resulted in a 62% increase in RTK activity and a 67% increase in PI-specific PLC activity. When EGF was added to incubations for RTK activity, it stimulated the RTK activity 40% in the control cells and 130% in the omega 3-treated cells. When EGF was added to incubations for PI-specific PLC activity, a 54% increase in PI-specific PLC activity was observed in control cells and a 94% increase in the omega 3-treated cells. Thus, treating EMT6 cells with omega 3 fatty acids seems to increase RTK activity and PI-specific PLC activity to a similar extent, but has differential effects on the ability of these enzyme activities to be stimulated by EGF.
...
PMID:Effects of omega 3 fatty acids on receptor tyrosine kinase and PLC activities in EMT6 cells. 945 35

Basic fibroblast growth factor (FGF-2) functions as a natural inducer of mesoderm, regulator of cell differentiation and autocrine modulator of cell growth and transformation. The FGF-2 signals are transduced through receptors with intrinsic protein tyrosine kinase activity. However, receptor binding and activation is governed by extracellular matrix, cell surface or soluble proteoglycans. This paper focuses on the role of proteoglycans synthesized by embryonic cells, embryoglycans, in FGF-2 signaling via FGF receptor-1 (FGFR-1). We found that embryoglycan ectodomain Lewis X, analog of developmentally regulated embryonic cell surface epitope TEC 1, promotes oligomerization of FGF-2 in the cell free chemical crosslinking. In vitro assays show that a large molar excess of extracellular Lewis X does not inhibit binding of FGF-2 to embryonic stem (ES) cells, but prevents the mitogenic effect of FGF-2. Western blot analysis of ES cells revealed the presence of abundant 52 kDa and trace amounts of 67 and 125 kDa isoforms of FGFR-1. However, none of these isoforms undergo any detectable changes in tyrosine phosphorylation under the conditions that modulate the mitogenic effect of FGF-2. Rather, a primary substrate of all receptor tyrosine kinases, phospholipase C gamma (PLC gamma), is activated by both FGF-2 and Lewis X. The combination, FGF-2 plus Lewis X, leads to weak inhibition, when compared with the effects of FGF-2 and Lewis X, respectively. In accordance, the level of phosphorylation of non-receptor tyrosine kinase c-Src is reduced in a reversed pattern to PLC(gamma). Furthermore, in this particular cell type we show the presence of activated forms of extracellular signal-related kinase (ERK) in all nontreated and treated cells. These findings demonstrate that embryoglycan ectodomains may act as negative regulators of FGF-2-induced ES cell proliferation, most likely through the FGFR-1-independent signaling pathway.
...
PMID:Embryoglycan ectodomains regulate biological activity of FGF-2 to embryonic stem cells. 973 Sep 86

Irreversible tyrosine modifications by inflammatory oxidants such as peroxynitrite (ONOO-) can affect signal transduction pathways involving tyrosine phosphorylation. The epidermal growth factor receptor (EGFR), a member of the c-ErbB receptor tyrosine kinase family, is involved in regulation of epithelial cell growth and differentiation, and possible modulation of EGFR-dependent signaling by ONOO- was studied. Exposure of epidermoid carcinoma A431 cells to 0.1-1.0 mM ONOO- resulted in tyrosine nitration on EGFR and other proteins but did not significantly affect EGFR tyrosine autophosphorylation. A high molecular mass tyrosine-phosphorylated protein (approximately 340 kDa) was detected in A431 cell lysates after exposure to ONOO-, most likely representing a covalently dimerized form of EGFR, based on immunoprecipitation and/or immunoblotting with alpha-EGFR antibodies and co-migration with ligand-induced EGFR dimers cross-linked with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. Covalent EGFR dimerization by ONOO- probably involved intermolecular dityrosine cross-linking and was enhanced after receptor activation with epidermal growth factor. Furthermore, irreversibly cross-linked EGFR was more extensively tyrosine-phosphorylated compared with the monomeric form, indicating that ONOO- preferentially cross-links activated EGFR. Exposure of A431 cells to ONOO- markedly reduced the kinetics of tyrosine phosphorylation of a downstream EGFR substrate, phospholipase C-gamma1, which may be related to covalent alterations in EGFR. Alteration of EGFR signaling by covalent EGFR dimerization by inflammatory oxidants such as ONOO- may affect conditions of increased EGFR activation such as epithelial repair or tumorigenesis.
...
PMID:Peroxynitrite induces covalent dimerization of epidermal growth factor receptors in A431 epidermoid carcinoma cells. 982 54

Fibroblast growth factors (FGFs) stimulate proliferation, differentiation and motility of different cell types. The cellular effects of FGF are transduced by its interaction with any one of four members of a family of high affinity, cell surface FGF receptors (FGFRs) that have autophosphorylating tyrosine kinase activity. Activation of FGFR causes release of various low molecular weight signaling molecules which are required for the pleotropic effects of FGFs. We report here that basic FGF plays critical role in membrane phospholipid hydrolysis in NIH 3T3 cells that are stably transfected with FGFR1. Upon binding to FGFR1, basic FGF stimulates cytosolic form of phospholipase A2 (cPLA2), phospholipase C-gamma1 (PLC-gamma1) and phospholipase D (PLD), the key enzymes for the production of various lipid second messengers, in a tyrosine kinase-dependent manner. In addition to tyrosine phosphorylation, cPLA2 catalytic activation requires serine phosphorylation by p42 mitogen-activated protein (MAP) kinase and possibly pertussis toxin-sensitive G-protein coupling. On the other hand, phosphatidyl inositol 4,5 bisphosphate (PIP2) hydrolysis requires direct phosphorylation at tyrosine residue of the PLC-gamma1 isozyme. The activation of PLD needs direct or indirect receptor tyrosine kinase and protein kinase C (PKC) activities. Additionally, it also requires botulinum toxin C-sensitive Rho-like G-protein activation. All these results suggest that the pleotropic effects of FGF are exerted through its tyrosine kinase receptors and individual effectors are activated via distinguishable signaling mechanisms according to the cell's need.
...
PMID:Basic fibroblast growth factor stimulates cytosolic phospholipase A2, phospholipase C-gamma1 and phospholipase D through distinguishable signaling mechanisms. 1049 74

No ligand has hitherto been designated for the Eph receptor tyrosine kinase family member, EphB6. Here, expression of an EphB6 ligand in the pro-B leukemic cell line, Reh, is demonstrated by binding of soluble EphB6-Fc fusion protein to the Reh cells. The ligand belongs to the subgroup of membrane spanning ligands, as suggested by the fact that phosphatidylinositol-specific phospholipase C treatment did not abrogate binding of EphB6-Fc. Two transmembrane Eph receptor ligands, ephrin-B1 and ephrin-B2, were identified in Reh cells. Analysis of EphB6-Fc fusion protein binding to ephrin-B1 or ephrin-B2 transfected COS cells revealed a high-affinity saturable binding between EphB6-Fc and ephrin-B2, but not with ephrin-B1. In mice, EphB6 has previously been shown to be expressed in thymus. Here, we show expression of EphB6 in human thymus, as well as the expression of ephrin-B2 in both human and mouse thymus. We conclude that ephrin-B2 may be a physiological ligand for the EphB6 receptor.
...
PMID:Ephrin-B2 is a candidate ligand for the Eph receptor, EphB6. 1064 35

Although fibroblast growth factor-2 (FGF-2) plays an important role in cardioprotection and growth, little is known about the signals triggered by it in the adult heart. We therefore examined FGF-2-induced effects on phosphoinositide-specific phospholipase C (PI-PLC) isozymes, which produce second messengers linked to the inotropic and hypertrophic response of the myocardium. FGF-2, administered by retrograde perfusion to the isolated heart, induced an increase in inositol-1,4,5-trisphosphate levels in the cytosol, as well as an increase in total PI-PLC activity associated with sarcolemmal and cytosolic fractions. Furthermore FGF-2 induced a time-dependent elevation in cardiomyocyte membrane-associated PLC gamma1 and PLC beta1 activities, assayed in immunoprecipitated fractions, and moreover, increased the membrane levels of PLC beta1 and PLC beta3. Activation of PLC beta is suggestive of FGF-2-induced cross-talk between FGF-receptor tyrosine kinase and G-protein-coupled signaling in adult cardiomyocytes and underscores the importance of FGF-2 in cardiac physiology.
...
PMID:Fibroblast growth factor-2 stimulates phospholipase Cbeta in adult cardiomyocytes. 1066 34


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

---