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)

Specimens of astrocytoma, oligodendroglioma and medulloblastoma were sequentially extracted with saline and saline-Triton X-100 buffers. Acetyl- (AChE) and butyrylcholinesterase (BuChE) activities were assayed in the soluble fractions, these being further analyzed to establish the distribution of molecular forms. All the tumors tested showed AChE and BuChE activities, the measured AChE/BuChE ratios being unrelated to the malignant grading. Hydrophilic and amphiphilic AChE and BuChE tetramers, amphiphilic AChE dimers and monomers, and hydrophilic BuChE monomers were identified in all the tumors analyzed. The amphiphilic behavior of the enzyme forms was assessed by sedimentation analysis and hydrophobic chromatography on phenyl-Agarose. A small fraction of glioma AChE monomers was released as, or transformed into, hydrophilic forms by incubation with phosphatidylinositol-specific phospholipase C (PIPLC). These data suggest that AChE monomers bearing distinct hydrophobic domains coexist in human glioma.
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PMID:Molecular forms of acetyl- and butyrylcholinesterase in human glioma. 871 Jan 79

Nerve growth factor (NGF) induces apoptosis in a human medulloblastoma cell line (MED283) engineered to express TrkA (MED283-TrkA) (Muragaki, Y., Chou, T. T., Kaplan, D. R., Trojanowski, J. Q., and Lee, V. M. (1997) J. Neurosci. 17, 530-542). To dissect the molecular signaling pathway that mediates this novel effect, specific receptor mutations in Trk have been employed. We showed that phosphorylation of tyrosine 490 is required for activation of phosphoinositide 3-OH kinase, whereas phosphorylation of tyrosine 785 is required for activation of phospholipase C-gamma. TrkA-mediated apoptosis was abolished when either the ATP-binding site or both tyrosines 490 and 785 were mutated. Because tyrosines 490 and 785 mediate redundant signaling through the Ras-extracellular signal-regulated kinase (Ras-ERK) pathway, we examined the role of Ras-ERK signaling in NGF-induced apoptosis. We found that MED283-TrkA cells expressing a dominant negative Ras inhibitor (N17Ras) failed to undergo ERK activation and apoptosis following NGF treatment, whereas the ERK kinase (mitogen-activated protein kinase kinase) inhibitors PD98059 and U0126 eliminated ERK activation but had no effect on apoptosis. We infer from these data that NGF-induced apoptosis is mediated by a novel Ras and/or Raf signaling pathway.
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PMID:A novel apoptotic pathway induced by nerve growth factor-mediated TrkA activation in medulloblastoma. 1061 52

Extracellular acidification accompanies neoplastic transformation of tissues and increases with tumor aggressiveness [1, 2]. The intracellular signaling cascade triggered by this process remains poorly understood and may be linked to recently discovered proton-activated G protein-coupled receptors such as OGR1 and G2A [3, 4]. Here, we report that OGR1 and G2A are expressed in human medulloblastoma tissue and its corresponding neuronal cell line. We show that extracellular acidification activates phospholipase C, IP(3) formation, and subsequent Ca2+ release from thapsigargin-sensitive stores in neurons. The number of responsive cells and the amount of Ca2+ released from stores correlated positively with the extent of extracellular acidification. Ca2+ release recruited the MEK/ERK pathway, providing a mechanistic explanation for how acidification stimulates cell growth. In addition, acidification activated Ca2+-permeable ion channels through a mechanism dependent on phospholipase C but independent of store depletion or a cytoplasmic Ca2+ rise. Hence, extracellular acidification, to levels seen in tumor tissue, activates temporally and spatially distinct pathways that elevate Ca2+ and may be directly relevant for tumor cell biology.
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PMID:Extracellular acidification elicits spatially and temporally distinct Ca2+ signals. 1848 12