High impact information on PLCD1

• Neither of the two mixtures of monoclonal antibodies nor the rabbit polyclonal antibodies directed against either PLC-I or PLC-II cross-reacted with PLC-III [1].
• The three enzymes were affected differently by bovine serum albumin: inhibition of PLC-I and activation of PLC-III were observed, whereas PLC-II was unaffected [1].
• We now report the purification of another form of inositolphospholipid-specific phospholipase C from bovine brain cytosol, designated PLC-III, and the comparison of the catalytic properties of the three isozymes [1].
• Approximately 450 micrograms of pure PLC-III was obtained from 36 bovine brains, and it had a final specific activity of 30-40 mumol of phosphatidylinositol hydrolyzed per min per mg of enzyme in the presence of 0.1% deoxycholate [1].
• We report here that adding 10-100 nm MARCKS-(151-175) to a subphase containing either PLC-delta or -beta inhibits hydrolysis of PIP(2) in a monolayer and that this inhibition is due to the strong binding of the peptide to PIP(2) [2].

Biological context of PLCD1

• These observations are consistent with the idea that the amino-terminal domain forms part of a PIP2 binding site, which anchors PLC-delta 1 to the membrane surface during processive hydrolysis of its substrate [3].
• This genomic sequence spans 13 kb of DNA and encoded 98.5% of the predicted coding sequence for the hamster PLC delta 1 cDNA within 15+ exons [4].
• Second messenger production from phosphoinositide hydrolysis is regulated by different pathways, such as G-proteins or tyrosine phosphorylation of phosphoinositide phospholipase C (PI-PLC) [5].

Anatomical context of PLCD1

• D-myo-inositol 1,4,5-trisphosphate inhibits binding of phospholipase C-delta 1 to bilayer membranes [6].
• Identification in bovine liver plasma membranes of a Gq-activatable phosphoinositide phospholipase C [7].
• We also show that antibodies raised against PLC alpha efficiently immunoprecipitate the 85-kDa PLC delta 1 isoform from bovine brain and Chinese hamster lung fibroblasts [8].
• These data provide strong evidence that the PLC alpha from sheep seminal vesicles is a proteolytic fragment of PLC delta 1 [8].
• This observation is shown to be the result of the differential loss, in both mutants, of one of two alleles for the hamster PLC delta 1 gene normally present in the parental cell line [4].

Associations of PLCD1 with chemical compounds

• A catalytic fragment of PLC-delta 1 that lacks a domain necessary for high affinity PIP2 binding was prepared as previously described (Cifuentes, M. E., Honkanen, L., and Rebecchi, M. J. (1993) J. Biol. Chem. 268, 11586-11593) [6].
• Proteolytic fragments of phosphoinositide-specific phospholipase C-delta 1. Catalytic and membrane binding properties [3].
• Hydrolysis of short acyl chain inositol lipids by phospholipase C-delta 1 [9].
• Bovine liver cytosol contains a phosphoinositide phospholipase C (PLCcyt) that is activated by guanosine 5'-O-(3-thio)triphosphate (GTP gamma S)-activated G-proteins from liver plasma membranes [10].
• The binding affinity of PLC-delta 1 for vesicles containing PC and PI(4,5)P2 was slightly diminished by inclusion of SPM in the lipid mixture, but not enough to account for the decreased rate of catalysis [11].

Analytical, diagnostic and therapeutic context of PLCD1

• Since gel filtration of PLC activity in wild type extracts gave Mr values similar to that of previously characterized PLCs (140,000-200,000), immunoblots with antibodies to bovine brain isoenzymes were used to show that the PLC activities obtained by anion exchange chromatography were PLC-delta and PLC-gamma [12].
• The fact that these monoclonal antibodies bind to different epitopes on the same enzyme allowed one to develop a highly specific and sensitive tandem radioimmunoassay for quantitating PLC-I, PLC-II, and PLC-III [13].

References