High impact information on GPLD1

• Expression of PI-G PLD complementary DNA in COS cells produced a protein that specifically hydrolyzed the inositol phosphate linkage of the PI-G anchor [1].
• A phosphatidylinositol-glycan-specific phospholipase D (PI-G PLD) that specifically hydrolyzes the inositol phosphate linkage in proteins anchored by phosphatidylinositol-glycans (PI-Gs) has recently been purified from human and bovine sera [1].
• Previous work has suggested that the glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) purified from bovine serum is inhibited by phosphatidic acid (PA) [2].
• Phosphatidic acid, lysophosphatidic acid, and lipid A are inhibitors of glycosylphosphatidylinositol-specific phospholipase D. Specific inhibition of a phospholipase by product analogues [2]?
• These data indicate that the resistance of cell membranes to the action of GPI-PLD is not entirely due to the action of serum or membrane-associated inhibitory factors [3].

Biological context of GPLD1

• Phosphorylation by PKA occurred in the 110 kDa native form of GPI-PLD as well as in multiple proteolytic degradation products and caused a significant decrease in enzyme activity [4].
• These lipidic fractions were partially sensitive to treatment with nitrous acid and to hydrolysis by glycosyl-phosphatidylinositol-specific phospholipase D from bovine serum [5].
• Studies of the role of the integrin EF-hand, Ca2+-binding sites in glycosylphosphatidylinositol-specific phospholipase D: reduced expression following mutagenesis of residues predicted to bind Ca2+ [6].
• Meanwhile, lysophosphatidylcholine (IC50, 25 microM) and phosphatidic acid (IC50, >100 microM), ionic amphiphiles, inhibited the GPI-PLD activity, which was determined in the presence of monooleoylglycerol as a detergent [7].

Anatomical context of GPLD1

• Treatment of intact ROS17/2.8, WISH or HeLa cells (or membrane fractions prepared from them) with GPI-PLD purified from bovine serum by immunoaffinity chromatography gave no detectable release of alkaline phosphatase into the medium [3].
• These data may account for the ability of endothelial and blood cells to retain GPI-anchored proteins on their surfaces in spite of the high levels of GPI-PLD present in plasma [3].
• It has been reported that mammalian serum, and to a lower extent mammalian liver, brain, pancreas, udder, and milk, contain glycosylphosphatidylinositol-specific phospholipase D activity [8].
• In situ hybridization experiments with a specific anti-sense RNA probe, derived from a bovine liver cDNA, revealed that glycosylphosphatidylinositol-specific phospholipase D mRNA is present in mast cells of the adrenal gland, lung, and liver [8].

Associations of GPLD1 with chemical compounds

• As with the cell membranes the reconstituted substrates exhibited marked resistance to the action of purified GPI-PLD which could be overcome by the inclusion of Nonidet P-40 [3].
• Triton X-100 was also able to dissociate aggregated GPI-PLD, however, it strongly inhibited enzyme activity at detergent concentrations above the critical micellar concentration [9].
• Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) was phosphorylated in vitro by cAMP-dependent protein kinase (PKA) and by tyrosine kinase [4].
• The enzymatic activity of purified GPI-PLD, which was depleted of divalent cations by pretreatment with EDTA, EGTA, or 1, 10-phenanthroline, could be completely restored with Zn2+ (and partially with Co2+), which indicates that Ca2+ can be removed from the protein without affecting its enzymatic activity [6].
• Presence of double bond in acyl chain, as exemplified by monooleoylglycerol or mono-11-eicosenoin, further enhanced the conversion by GPI-PLD [7].

Other interactions of GPLD1

• Glycosyl-phosphatidylinositol-specific phospholipase D. Interaction with and stimulation by apolipoprotein A-I [9].

Analytical, diagnostic and therapeutic context of GPLD1

• Northern blot analysis of total bovine liver RNA demonstrated two distinct glycosylphosphatidylinositol-specific phospholipase D mRNAs of approximately 3.3 kb and 4 kb length suggesting that two forms of the enzyme may exist [8].

References