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

Here we present evidence that exposure of DT40 lymphoma B-cells to low energy electromagnetic fields (EMF) results in activation of phospholipase C-gamma 2 (PLC-gamma2), leading to increased inositol phospholipid turnover. PLC-gamma2 activation in EMF-stimulated cells is mediated by stimulation of the Bruton's tyrosine kinase (BTK), a member of the Src-related TEC family of protein tyrosine kinases, which acts downstream of LYN kinase and upstream of PLC-gamma2. B-cells rendered BTK-deficient by targeted disruption of the btk gene did not show enhanced PLC-gamma2 activation in response to EMF exposure. Introduction of the wild-type (but not a kinase domain mutant) human btk gene into BTK-deficient B-cells restored their EMF responsiveness. Thus, BTK exerts a pivotal and mandatory function in initiation of EMF-induced signaling cascades in B-cells.
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PMID:Electromagnetic field-induced stimulation of Bruton's tyrosine kinase. 957 94

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.
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PMID:Embryoglycan ectodomains regulate biological activity of FGF-2 to embryonic stem cells. 973 Sep 86

Megakaryocytopoiesis is the process by which bone marrow progenitor cells develop into mature megakaryocytes, which in turn produce platelets required for normal hemostasis. The development of this hematopoietic lineage depends on a variety of growth factors and cytokines. Growth factor-dependent tyrosine kinase receptors important in megakaryocytopoiesis include c-Kit, fibroblast growth factor receptor, the RON receptor, and the macrophage colony-stimulating factor receptor. Binding of growth factors to their respective receptors results in receptor dimerization and subsequent autophosphorylation on tyrosine residues. Tyrosine autophosphorylations become sites of association for cytoplasmic signaling molecules via their SH2 domains. Some of these molecules are themselves cytoplasmic tyrosine kinases such as the Src kinases, TEC, and CHK. Others are molecules such as phospholipase C-gamma, phosphoinositol 3-kinase, Shc, GTPase-activating protein, and the SH2-containing tyrosine phosphatases SHP-1 and SHP-2. These molecules generate second messengers, regulate the phosphorylation of other downstream molecules, and also regulate the phosphorylation of the receptor itself. The different cytoplasmic components activate pathways involved in either changes in cell growth or changes in the cytoskeleton that affect maturation of the cell. Cytokine receptors also generate signals involved in growth and differentiation. Some of these second messengers overlap with those of the receptor tyrosine kinases. Others, such as the JAKs/STATs, are involved in transcriptional control and are unique to the signaling mediated by cytokine receptors. We describe the contribution of these different signals to the growth/differentiation processes of megakaryocytes. We also describe the contribution of receptor and nonreceptor tyrosine phosphatases to these processes. Lastly, we have compiled selected methods related to the study of protein phosphorylation in megakaryocytes.
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PMID:Regulation of megakaryocytopoiesis and platelet production by tyrosine kinases and tyrosine phosphatases. 1008 Sep 10

Previous studies using cytochalasins and latrunculin B, inhibitors of actin polymerization, showed that filamentous (F)-actin had a negative regulatory role in Fc epsilon receptor I (Fc epsilon RI) signaling. How F-actin is involved in regulating the activation of mast cells is unknown. In this study we investigated the role of F-actin in mast cell activation induced by aggregation of the glycosylphosphatidylinositol (GPI)-anchored proteins Thy-1 and TEC-21, and compared it to activation via Fc epsilon RI. Pretreatment of rat basophilic leukemia cells with latrunculin B inhibited the Thy-1-induced actin polymerization and elevated the Thy-1-mediated secretory and calcium responses. Inhibition of actin polymerization followed by Thy-1 aggregation resulted in an increased tyrosine phosphorylation of Syk, phospholipase C gamma (PLC gamma), Gab2 and linker for activation of T cells (LAT) adapters, and some other signaling molecules. Enzymatic activities of phosphatidylinositol 3-kinase, PLC gamma, and phosphatase SHP-2 were also up-regulated, but tyrosine phosphorylation of ezrin was inhibited. Similar changes were observed in Fc epsilon RI-activated cells. Significant changes in intracellular distribution, tyrosine phosphorylation, and/or enzymatic activities of signaling molecules occurred in latrunculin-pretreated cells before cell triggering. The combined data suggest that actin polymerization is critical for setting the thresholds for mast cell signaling via aggregation of both Fc epsilon RI and GPI-anchored proteins.
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PMID:Involvement of filamentous actin in setting the threshold for degranulation in mast cells. 1516 32

The TEC-family protein tyrosine kinases ITK, RLK and TEC have been identified as key components of T-cell-receptor signalling that contribute to the regulation of phospholipase C-gamma, the mobilization of Ca(2+) and the activation of mitogen-activated protein kinases. Recent data also show that TEC kinases contribute to T-cell-receptor-driven actin reorganization and cell polarization, which are required for productive T-cell activation. Functional studies have implicated TEC kinases as important mediators of pathways that control the differentiation of CD4(+) T helper cells. Here, we review studies of signalling pathways that involve TEC kinases and how these pathways might contribute to the regulation of T-helper-cell differentiation and function.
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PMID:TEC-family kinases: regulators of T-helper-cell differentiation. 1580 48