Disease relevance of PCTP

• Bovine liver phosphatidylcholine transfer protein (PC-TP) has been expressed in Escherichia coli and purified to homogeneity from the cytosol fraction at a yield of 0.45 mg PC-TP per 10 mg total cytosolic protein [1].
• The contribution of the phosphatidylcholine specific exchange protein to the total phosphatidylcholine transfer activity was determined in normal and host liver and in the hepatomas 7777 and 9633 with the aid o f a phosphatidylcholine exchange protein specific antiserum [2].

High impact information on PCTP

• The phosphatidylcholine specific transfer protein (PCTP) from bovine liver was used to retailor the molecular species composition of phosphatidylcholine (PC) in the membrane of normal (AA) and sickleable (SS) human erythrocytes [3].
• Efficient synthesis of this lipid from phosphatidylinositol has been proposed to require the presence of a phosphatidylinositol/phosphatidylcholine transfer protein (PITP), which transfers phosphatidylinositol and phosphatidylcholine between membranes, but the mechanism by which PITP exerts its effects is currently unknown [4].
• These results suggest that phosphatidylcholine transfer protein permits phosphatidylcholine synthesis to proceed further [5].
• The effect of rat liver phosphatidylcholine transfer protein on the incorporation of CDP-choline and dioleoylglycerol into phosphatidylcholine catalyzed by rat liver microsomal CDP-choline: 1,2-diacyl-sn-glycerol cholinephosphotransferase was studied [5].
• Analysis by confocal laser scanning microscopy showed that PC-TP was evenly distributed throughout the cytosol with an apparently elevated level in nuclei [6].

Biological context of PCTP

• Towards the end of embryonic development, just before term, high levels of PC-TP RNA were found in the liver [7].
• The predicted amino acid sequence was 90% similar (81% identical) to the corresponding sequence of bovine liver PC-TP, demonstrating that PC-TP is conserved among mammalian species [7].
• PC-TP RNA was present in embryos at all stages of development as early as the embryonic stem cell, suggesting a role for PC-TP in cell growth and differentiation [7].
• Given the proposed function of PC-TP in lipid metabolism, we have tested a number of compounds (phorbol ester, bombesin, A23187, thrombin, dibutyryl cyclic AMP, oleate, clofibrate, platelet-derived growth factor, epidermal growth factor, and hydrogen peroxide) for their ability to affect intracellular PC-TP distribution [6].
• The data are discussed in terms of the structural organization of the sn-1 and sn-2 acyl binding sites of PC-TP and PI-TP.(ABSTRACT TRUNCATED AT 250 WORDS)[8]

Anatomical context of PCTP

• In addition to adult liver, high levels of PC-TP RNA were also found in kidney and testis [7].
• PC-TP from the cytosol contains phosphatidylethanolamine (PE) and phosphatidylglycerol (PG) with a preference for the di-monounsaturated species over the saturated species as determined by fast atom bombardment mass spectrometry (FAB-MS) [1].
• In addition, active PC-TP was obtained from inclusion bodies [1].
• Only clofibrate (100 microM) was found to have an effect, with PC-TP moving to mitochondria within 5 min of stimulation [6].
• To get more insight into its physiological function, we have studied the localization of PC-TP by microinjection of fluorescently labeled PC-TP in foetal bovine heart endothelial (FBHE) cells and by expression of an enhanced yellow fluorescent protein-PC-TP fusion protein in FBHE cells, human umbilical vein endothelial cells, and HepG2 cells [6].

Associations of PCTP with chemical compounds

• An essential factor in the activation of PC-TP was phosphatidylcholine (PC) present in the folding buffer [1].
• The complete primary structure of the phosphatidylcholine-transfer protein from bovine liver. Isolation and characterization of the cyanogen bromide peptides [9].
• Determination of the acyl chain specificity of the bovine liver phosphatidylcholine transfer protein. Application of pyrene-labeled phosphatidylcholine species [10].
• The transport of pyrene-labeled triglyceride from donor particles to MTP was rapid, while phosphatidylcholine transfer had fast and slow phases [11].
• Modification by phenylisothiocyanate inhibits the phosphatidylcholine-transfer protein from bovine liver [12].

Physical interactions of PCTP

• PC-TP is structurally homologous to the lipid-binding domain of the steroidogenic acute regulatory protein (Nat. Struct. Biol. 7 (2000) 408) [1].

Other interactions of PCTP

• Submicellar bile salts stimulate phosphatidylcholine transfer activity of sterol carrier protein 2 [13].

Analytical, diagnostic and therapeutic context of PCTP

• By Southern blot analysis, evidence was obtained for the presence of a single bovine PC-TP-encoding gene [7].

References