Disease relevance of PLCG2

• The generation of these substances from membranes by insulin can be reproduced by addition of a phosphatidylinositol-specific phospholipase C purified from Staphylococcus aureus [1].
• The enzyme was solubilized using phosphatidylinositol-specific phospholipase C (Bacillus thuringiensis), indicating that bovine lung amino-peptidase P is attached to membranes via a glycosylphosphatidylinositol anchor [2].
• These observations indicate that G418 is an allosteric activator of Bacillus cereus PI-PLC [3].
• The regulation of parathyroid hormone secretion by the chief cells of the parathyroid is mediated by a 7-transmembrane (7-TM) Ca2+-sensing receptor (CaR), which signals via activation of pertussis toxin-insensitive G proteins, causing stimulation of phosphatidylinositol-specific phospholipase C (PI-PLC) [4].
• The construction of four vectors for high-level expression in Escherichia coli of the phosphatidylinositol-specific phospholipase C from Bacillus cereus or Bacillus thuringiensis is described [5].

High impact information on PLCG2

• Here we report the cloning of a bovine brain complementary DNA encoding an enzyme PLC-148 that is characterized by calcium-dependent and phosphatidylinositol-specific phospholipase C activity when expressed in mammalian cells [6].
• The production of the second messenger molecules diacylglycerol and inositol 1,4,5-trisphosphate is mediated by activated phosphatidylinositol-specific phospholipase C (PLC) enzymes [6].
• Together, these data suggest that permanent sequential activation of both PI3K and PI-PLC is necessary for the dramatic reorganization of the actin cytoskeleton in oncogene-transformed fibroblasts, resulting in constitutive ruffling and macropinocytosis [7].
• Implied in these observations are the following: (i) in powerful inhibitors an active site residue probably interacts with the equatorially oriented fluoro substituent; (ii) substrate recognition requires a negative charge on the phosphoryl at the Ins-1 position, and (iii) a GPI is better substrate than PI, for PI-PLC [3].
• Aminoglycoside antibiotics kanamycin A, gentamycin, and G418 stimulated PI-PLC cleavage of the GPI anchor of variant surface glycoprotein (VSG) from Trypanosoma brucei 2- to 4-fold [3].

Chemical compound and disease context of PLCG2

• Treatment of the LPGs with phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis liberates a ceramide substituent [8].
• Bovine erythrocytes were treated with each of three bacterial phospholipases C; phosphatidylcholine-hydrolyzing phospholipase C (PCase) of Clostridium perfringens, sphingomyelinase C (SMase) of Bacillus cereus and phosphatidylinositol-specific phospholipase C (PIase) of Bacillus thuringiensis [9].

Biological context of PLCG2

• The inhibitory lipids did not affect substrate availability nor did they reduce hydrolysis of variant surface glycoprotein by a bacterial phosphatidylinositol-specific phospholipase C. Studies with a wide range of other lipids, detergents, and phosphate esters indicated that inhibition was specific for lipids containing a phosphomonoester group [10].
• The 180-kDa TGF-beta 1 binding protein and the 60- and 140-kDa TGF-beta 2 binding proteins can be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, suggesting that these proteins are attached to the plasma membrane through a phosphatidylinositol anchor [11].
• It is reported here that there is a strong dependence on methylation for activating both PIPLC and PI3K [12].
• It is possible that inhibition of PtdInsPLC is responsible for the cell growth inhibition and antitumour properties of the peptide compounds [13].
• Three naturally occurring peptide inhibitors of PtdInsPLC have been identified, myroridin K, streptothricin B and edeine, with IC50 values of 8.3, 6.7 and 16.1 microM, respectively [13].

Anatomical context of PLCG2

• Treatment of the crude membrane fraction and purified synaptic plasma membranes with phosphatidylinositol-specific phospholipase C revealed that isoforms of brevican are indeed glycosylphosphatidylinositol-anchored to the plasma membrane [14].
• Incubation of fragmented chromaffin granule membranes with phosphatidylinositol-specific phospholipase C led to no solubilization of dopamine beta-hydroxylase activity [15].
• The aerolysin receptor was shown to be anchored in the same way by treating rat erythrocytes with phosphatidylinositol-specific phospholipase C. This caused the selective release of the receptor and a reduction in the rodent cells' sensitivity to aerolysin [16].
• Treatment of intact 3T3 cells or 3T3 cell membranes with either broad and phosphatidylinositol-specific phospholipase C enzymes suggested that the antigenic material most likely existed as an integral membrane molecule, or associated as a multimeric complex, and was not anchored at the cell surface by a phospholipid [17].
• Incubation at 37 degrees C or treatment of granule membranes of chromaffin cells with Staphylococcus aureus phosphatidylinositol-specific phospholipase C converted from an amphiphilic to a hydrophilic form two proteins with molecular masses of 82 and 68 kDa respectively [18].

Associations of PLCG2 with chemical compounds

• Protein-protein interactions between MBP and PI-PLC have been demonstrated both immunologically and by sucrose density gradients [19].
• These results suggest that the natural chiro-inositol derivatives should have the 1L-configuration if they are produced by PI-PLC, which is in contrast to the 1D-configuration reported by others [20].
• Furthermore this protein could be released from the particulate pellet after treatment with phosphatidylinositol-specific phospholipase C, suggesting its anchorage via a phosphatidylinositol glycan linkage in the plasma membrane [21].
• Phospholipids chiral at phosphorus. Stereochemical mechanism for the formation of inositol 1-phosphate catalyzed by phosphatidylinositol-specific phospholipase C [22].
• On the other hand, 1D-chiro-PI was found to be resistant to PI-PLC [20].

Regulatory relationships of PLCG2

• Peptides containing the MBP sequences consisting of residues 24-33 and 114-122 stimulated the PI-PLC but were less effective than the intact protein [19].
• Moreover, phosphatidylinositol-specific phospholipase C (PIPLC) treatment of rat cells markedly inhibited the aggrecanase response to IL-1b and RA [23].

Other interactions of PLCG2

• Treatment of membranes with a phosphatidylinositol-specific phospholipase C did not remove TH, ruling out the possibility of a glycosyl phosphatidyl anchor [24].
• Phosphatidylinositol-specific phospholipase C solubilized G2 acetylcholinesterase from plasma membranes of chromaffin cells [25].
• The phosphatidylinositol-specific phospholipase C released the ecto-5'-nucleotidase from the chromaffin cells in culture, thus suggesting an anchorage through phosphatidylinositol to plasma membranes [26].
• After treatment with phosphatidylinositol-specific phospholipase C, the enzyme is transformed into a hydrophilic form, for which interactions with laminin and fibronectin could also be demonstrated by the dot-blot technique [27].

Analytical, diagnostic and therapeutic context of PLCG2

• After treatment with phosphatidylinositol-specific phospholipase C, parasite lysates were analyzed with antibodies against the cross-reacting determinant of glycosylphosphatidylinositol anchors [28].
• The size and SDS-PAGE pattern of the proteins were different among cell lines but they were liberated from the cells by the treatment with phosphatidylinositol-specific phospholipase C. The toxin appeared to target and utilize detergent resistant membranes (DRMs) for binding and subsequent oligomerization [29].
• Phosphatidylinositol-specific phospholipase C was purified to homogeneity from soluble fraction of bovine platelets by ammonium sulfate fractionation, hydrophobic chromatography, DEAE ion exchange chromatography and gel filtration [30].
• The amphiphilic eNT dimers or monomers were converted into their hydrophilic variants with phosphatidylinositol-specific phospholipase C. SDS-PAGE plus Western blot showed 68 kDa subunits, regardless of the addition of beta-mercaptoethanol to the SDS mixture [31].
• The sucrose gradient centrifugation showed that PI-PLC was enriched in membrane fraction distinct from mitochondria and acrosomes [32].

References