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)

The transforming protein of polyomavirus, middle T (mT), forms a complex with two cellular enzymes: the protein tyrosine kinase pp60c-src and a phosphatidylinositol (PtdIns) 3-kinase. A mutant virus, Py1178T, encodes an mT protein which associates with and activates pp60c-src to the same extent as the wild type but fails to associate with PtdIns 3-kinase. To investigate relationships between activation of pp60c-src, association of PtdIns 3-kinase, and cellular levels of the second messenger inositol 1,4,5-trisphosphate (InsP3), we examined the effects of wild-type and mutant mT proteins on inositol metabolism in rat and mouse fibroblasts. Expression of either wild-type or 1178T mT caused a 300 to 500% increase in the InsP3 level. Cells transformed by Rous sarcoma virus also showed similar increases in InsP3 levels. Mutant mT proteins which failed to activate pp60c-src (NG59 and 1387T) had no effect on InsP3 levels. Pulse-chase experiments with [3H]inositol showed that the turnover of phosphoinositides was increased in cells transformed by either wild-type polyomavirus or Py1178T as compared with the normal parent cell line. The turnover of inositol phosphates was unchanged upon transformation. These data indicate that cells expressing either wild-type or mutant 1178T mT or pp60v-src exhibit elevated levels of InsP3 because of activation of phospholipase C. This activation appears to depend, directly or indirectly, upon activation of pp60src protein kinase activity. Activation of pp60c-src and elevation of InsP3 content are not sufficient for full transformation. Full transformation also requires the association of mT-pp60c-src complexes with PtdIns 3-kinase.
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PMID:Inositol trisphosphate levels in cells expressing wild-type and mutant polyomavirus middle T antigens: evidence for activation of phospholipase C via activation of pp60c-src. 215 7

We have examined polyphosphoinositide turnover in a Rat-1 fibroblast line infected with a temperature-sensitive mutant (ts LA24) of the Rous sarcoma virus (RSV). When ts LA24-infected cells are shifted from the non-permissive to the permissive temperature, a rapid and sustained activation of phospholipase C (PLC) is observed. Normal and wild-type RSV-infected Rat-1 cells do not show any PLC activation upon temperature shiftdown. Pre-treatment of ts LA24-infected fibroblasts with tetrodotoxin (a Na+ channel inhibitor) or incubation in Na+-free medium significantly prevent temperature shiftdown-induced PLC activation. Therefore, we conclude that PLC activation occurs concomitantly with pp60v-src expression, and hypothesize that pp60v-src-related membrane depolarization is the causal link between pp60v-src tyrosine kinase activity and stimulation of polyphosphoinositide metabolism. Finally, we discuss the relationship between the phenomena we have observed and the mechanism of action of the ras oncogene.
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PMID:Polyphosphoinositide metabolism is rapidly stimulated by activation of a temperature-sensitive mutant of Rous sarcoma virus in rat fibroblasts. 283 May 81

Phosphatidylinositol (PI) synthesis was activated in Rous sarcoma virus-infected NIH3T3 or activated erbB2-transformed NIH3T3 cells. The in vitro activity of CDP-DG:inositol transferase prepared from these cells was also higher than that from normal parent NIH3T3 cells, although phospholipase C and PI kinase activities were not significantly different among these cells. A tyrosine kinase inhibitor, erbstatin, inhibited the PI synthesis in cultured cells, suggesting that Src and ErbB2-associated tyrosine kinases are involved in activation of CDP-DG:inositol transferase in these cell lines.
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PMID:Enhancement of CDP-DG:inositol transferase activity in src- and erbB2-transformed cells. 790 54

A tyrosine kinase inhibitor, genistein, caused the subcellular translocation of phosphoinositide-specific phospholipase C (PLC) activity from membrane fractions to cytosolic fractions in rat 3Y1 fibroblasts and their transformants by Rous sarcoma virus, SR-3Y1. The ratio of PLC activities associated with the membrane fractions to those of the homogenate fractions was greater in SR-3Y1 (32.6%) than in 3Y1 (20.8%) whereas membrane-associated PLC activities were strikingly reduced to the same levels in both cells by treatment with genistein. Moreover, it was found by immunoblotting analyses of membrane fractions that the amounts of PLC-gamma 1 isozyme were reduced to 20.4% of initial level in SR-3Y1 and to 30.2% of that in 3Y1 cells. While the levels of PLC-delta, another detectable PLC isozyme, were not altered by genistein suggesting that tyrosine kinase plays an important role in the association of PLC-gamma 1 with membranes. PLC-gamma 1 molecules were detected in anti-p60arc antibody immunoprecipitates of both 3Y1 and SR-3Y1 cells. The amounts of PLC-gamma 1 co-immunoprecipitating with src kinases were higher in SR-3Y1 than 3Y1 cells and were reduced in both cell types by treatment with genistein. In addition, it was confirmed that PLC-gamma 1 purified from rat liver was phosphorylated at a tyrosine residue and associated with viral src kinase and that src kinases associated with the recombinant SH2 region of PLC-gamma 1, expressed in Escherichia coli, depending upon phosphorylation of tyrosine residues. These findings suggest that both viral and cellular src kinases associate with PLC-gamma 1 and may mediate cellular signaling in normal and transformant cell growth.
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PMID:Phospholipase C-gamma 1 associates with viral and cellular src kinases. 838 73

This paper presents the partial characterization and the identification of an 80-kDa protein detected in bull spermatozoa using a monoclonal antibody directed against a 16-amino acid long peptide from the N-terminal domain of the protooncogene p60(src) from the Rous Sarcoma Virus When subjected to two-dimensional electrophoresis, this 80-kDa protein migrated as several isoforms, with an isoelectric point ranging from 7.4 to 8.2. Amino acid sequence analysis of a peptide obtained following trypsin digestion of the bull sperm protein showed homology to the PH-20/hyaluronidase precursor sperm protein. As for PH-20, this bull sperm 80-kDa protein is located at the plasma membrane surface in the postacrosomal region of the head. An increased immunolabeling in the anterior head region of fixed/permeabilized spermatozoa was observed when these cells were incubated under capacitating conditions, whereas most sperm cells challenged with the calcium ionophore A23187 to acrosome react lost their labeling almost completely. As for the PH-20 protein, the 80-kDa bull sperm protein possesses a hyaluronidase activity that is higher at pH 7.0 than at pH 4.0 in an in-gel assay. Unlike what has been observed in the guinea pig, mouse, and human PH-20, this 80-kDa protein was not released from the surface of bull spermatozoa by treatment with phosphatidylinositol-specific phospholipase C or with trypsin. However, this protein was not sedimented by a 100,000 x g centrifugation after nitrogen cavitation, which suggests that the 80-kDa protein is loosely attached to the sperm membrane by a yet-unknown mechanism. These results suggest that the 80-kDa bull sperm protein shares many homologies with the sperm PH-20 protein reported in the literature and, most likely, is the bull sperm homologue of the PH-20.
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PMID:Characterization of an 80-kilodalton bull sperm protein identified as PH-20. 1146 35