Disease relevance of PCSK7

• In conclusion, among the known members of the subtilisin family, only furin and LPC/PC7 fulfill the requirements of a protease responsible for in vivo activation of HIV envelope glycoproteins [1].
• Furin- and LPC/PC7-catalyzed cleavage of HIV-1 gp160 resulted in biologically active envelope protein [1].
• A new member of the proprotein convertase gene family (LPC) is located at a chromosome translocation breakpoint in lymphomas [2].
• A new member of the proprotein convertase gene family (LPC) has been identified at a chromosome translocation breakpoint occurring in a high grade lymphoma [2].
• The bacterial, recombinant prosegments were also used to generate specific antisera, allowing us to study the intracellular metabolic fate of the prosegments of furin and PC7 expressed via vaccinia virus constructs [3].

Psychiatry related information on PCSK7

• Within-group comparisons revealed that only the PTSD group but not the other groups showed a differentiation between trauma-specific and neutral questions with respect to the LPC, tCNV and P300 [4].
• In this study we investigated the effect of short- and long-term F0 measures on perceived emotional stress using stimuli synthesized with the LPC coefficients of a steady vowel and varying F0 tracks [5].
• More specifically, we tested the hypothesis that a pleasant odor could have effects on face perception: behavioral effects on subjective emotional estimation of faces, and on associated response times, and electrophysiological effects on the N400 and late positive complex or LPC [6].
• Compatibility among a sample of 52 elite tennis coach/player dyads was assessed using a sport adapted version of Schutz's (1966) Fundamental Interpersonal Relations Orientation-Behaviour (FIRO-B), a sport adapted version of Fiedler's (1967) Least Preferred Co-worker scale (LPC), and Chelladurai and Saleh's (1980) Leadership Scale for Sport (LSS) [7].

High impact information on PCSK7

• The ability of LPC-treated quiescent nuclei to undergo DNA replication was reversed by resealing permeable nuclear membranes with Xenopus egg membranes prior to extract incubation demonstrating that the effect of LPC treatment is at the level of the nuclear membrane [8].
• The gene for PC7 (Pcsk7) was mapped to mouse chromosome 9 by linkage analysis of an interspecific backcross DNA panel [9].
• cDNA structure, tissue distribution, and chromosomal localization of rat PC7, a novel mammalian proprotein convertase closest to yeast kexin-like proteinases [9].
• We assayed LAT in RBC membranes from Ch-loaded RBCs, using [14C]arachidonoyl CoA as precursor, and found similar decreased LAT activity at concentrations of 1-palmitoyllysophosphatidylcholine (LPC) from 1 to 30 micromol/L [10].
• The effects of lysolecithin (LPC) on aggregation, serotonin release, shape, and lysis of rabbit, pig, or human platelets in platelet-rich plasma (PRP) or Tyrode albumin solution were examined during prolonged incubation [11].

Chemical compound and disease context of PCSK7

• Comparative functional role of PC7 and furin in the processing of the HIV envelope glycoprotein gp160 [12].
• In addition, the C5 structure lends insight into the site of HIV envelope protein maturation by the host enzymes furin and PC7, which provides other possible targets for drug therapies [13].
• We now demonstrate that LPC also induces release of taurine under isotonic conditions in mouse fibroblast (NIH/3T3) and Ehrlich ascites tumor cells [14].
• Of those remaining parameters, the LCAT activity was increased as the severity of coronary atherosclerosis increased and the changes in the activity of this enzyme were appropriately reflected by increases in LPC concentration and decreases in the proportion of the plasma cholesterol unesterified [15].

Biological context of PCSK7

• PC7/8, in contrast, is detected throughout the epidermis with antibodies to both the transmembrane and active site and no soluble form observed [16].
• Biosynthesis, distinct post-translational modifications, and functional characterization of lymphoma proprotein convertase [17].
• Finally, substrate specificity of LPC is similar to that of furin but not identical [17].
• Altogether, our results give evidence of a genomic instability of this area of 11q23 and show that Pafah1a2 and not LPC is the gene disrupted by the translocation, suggesting that deregulated Pafah1a2 may have a role in lymphomagenesis [18].
• Here we show that LPC consists of at least 16 exons covering 25 kb, and that there is a partial duplication, involving mobile genetic elements and containing LPC exons 13-17 in a tail-tail configuration at 65 kb downstream [18].

Anatomical context of PCSK7

• As far as subcellular localization is concerned, immunocytochemical, ultrastructural, and biochemical analyses show that LPC is concentrated in the trans-Golgi network, associated with membranes, and not secreted [17].
• Prodomain removal is shown to be required for LPC to exit the endoplasmic reticulum [17].
• The data demonstrate that PC7 can cleave specifically and in a cell-type specific manner gp160 into gp120gp41, suggesting that both furin and PC7 are so far the major PC-like candidate gp160 convertase in T4 lymphocytes [12].
• Here we demonstrate that the unglycosylated precursor form of LPC is localized in the cytosol due to the absence of a signal peptide [19].
• This change was also shown both by introducing [gamma-32P]ATP and Mg2+ into MRC-5 fibroblasts permeabilized by LPC after stimulation by IL-1, and by adding the labeled ATP and Mg2+ to cell extracts [20].

Associations of PCSK7 with chemical compounds

• No statistically significant correlation was found between the levels of steroid receptors and the expression of human furin, PCI and PC7 genes [21].
• For optimal LPC substrate processing activity, an arginine at position P-6 is preferred over an arginine at P-4 [17].
• Lymphoma proprotein convertase (LPC) is a subtilisin-like serine protease of the mammalian proprotein convertase family [19].
• Palmitoylation of LPC was found to be sensitive to the protein palmitoyltransferase inhibitor tunicamycin but not cerulenin [22].
• When tested against PC7, these succinoylated derivatives of andrographolide also displayed strong inhibitory action, with Ki values again in the low micromolar range [23].

Enzymatic interactions of PCSK7

• In this report, we examined the capability of the newly cloned convertase PC7 to cleave gp160 into gp120/gp41 and compared it to furin [12].

Other interactions of PCSK7

• Northern blot analysis revealed that PACE4, furin and PC8 of the SPC family were expressed in HepG2 cells as well as in the liver [24].
• We have identified the proprotein-convertases PC7 and furin to be involved in maturation of TACE [25].
• Using a reducible cross-linker, we found that glycosylated pro-LPC is associated with the molecular chaperone BiP [19].
• Short Polybasic Peptide Sequences Are Potent Inhibitors of PC5/6 and PC7: Use of Positional Scanning-Synthetic Peptide Combinatorial Libraries as a Tool for the Optimization of Inhibitory Sequences [26].

Analytical, diagnostic and therapeutic context of PCSK7

• Northern blot analyses revealed that furin and the recently discovered protease LPC/PC7 were the only subtilisin-like enzymes transcribed in such cells [1].
• By using reverse transcription-coupled PCR on rat anterior pituitary RNA, we isolated a 285-bp cDNA coding for a novel subtilisin/kexin-like protein convertase (PC), called rat (r) PC7 [9].
• Healthy men (n = 12) participated in a double-blind, randomized, crossover study in which 3 olive oils with low (LPC), moderate (MPC), and high (HPC) phenolic content were given as raw doses (25 mL/d) for 4 consecutive days preceded by 10-d washout periods [27].
• The pattern of changes induced by apheresis in plasma PC, SM and LPC levels was mimicked by changes in RBCM phospholipids [28].
• A molecule isolated from the peritoneal fluids of women undergoing laparoscopy for in-vitro fertilization techniques has been chemically characterized and identified as 1-palmitic-3-phosphorylcholine (lysophosphatidylcholine, LPC) [29].

References