The first seven members of the proprotein convertase (PC) family activate protein precursors by cleavage after basic residues. While PC7 has no known specific substrates, it shows redundancy with other PCs. A genome-wide association study suggested t
TY - JOUR. T1 - Sorting of PC2 to the regulated secretory pathway in AtT20 cells. AU - Taylor, N A. AU - Jan, G. AU - Scougall, K T. AU - Docherty, K. AU - Shennan, K I. PY - 1998/10. Y1 - 1998/10. N2 - PC2 and PC3 are neuroendocrine specific members of the eukaryotic subtilisin-like proprotein convertase (PC) family. Both are sorted via the regulated secretory pathway into secretory granules. In order to identify sequences in PC2 which are involved in targeting to the regulated secretory pathway we expressed a series of PC2 cDNAs containing mutations in the C terminal or propeptide domains in the mouse corticotrophic AtT20 cell line. Sorting of endogenous PC3 was used as a control. PC2 and PC3 were secreted with similar kinetics and sorted to secretory granules with similar efficiencies. Deletions of up to 50 amino acids from the C-terminus of proPC2 had no effect on secretion or sorting, but larger deletions completely prevented maturation or secretion. Two large deletions within the ...
Proprotein Convertase Subtilisin/Kexin Type 9 (Proprotein Convertase 9 or Neural Apoptosis-Regulated Convertase 1 or PCSK9 or EC 3.4.21.) - Pipeline Review, H1 2016 Proprotein Convertase - Market research report and industry analysis - 10197474
The FDA recently announced approval of two cholesterol lowering drugs which both work by inhibiting PCSK9 or proprotein convertase subtilisin/kexin type 9. PCSK9 is an enzyme from the subtilisin-like proprotein convertase family which include proteases that process proteins trafficking through various constitutive secretory pathways. PCSK9 increases blood cholesterol levels by binding to low densitiy lipoprotein (LDL) receptors, targeting them for lysosomal…
This gene encodes a member of the subtilisin-like proprotein convertase family, which includes proteases that process protein and peptide precursors trafficking through regulated or constitutive branches of the secretory pathway. The encoded protein undergoes an initial autocatalytic processing event in the ER to generate a heterodimer which exits the ER and sorts to subcellular compartments where a second autocatalytic even takes place and the catalytic activity is acquired. The protease is packaged into and activated in dense core secretory granules and expressed in the neuroendocrine system and brain. This gene encodes one of the seven basic amino acid-specific members which cleave their substrates at single or paired basic residues. It functions in the proteolytic activation of polypeptide hormones and neuropeptides precursors. Mutations in this gene have been associated with susceptibility to obesity and proprotein convertase 1/3 deficiency. Alternatively spliced transcript variants ...
Khan AR, Bavishi C, Riaz H, Farid TA, Khan S, Atlas M, Hirsch G, Ikram S, Bolli R. Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors. Circ Cardiovasc Qual Outcomes. 2017 Jan;10(1). pii: e003153. doi: 10.1161/CIRCOUTCOMES.116.003153. PubMed PMID: 28073851 ...
Proprotein convertase involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues (By similarity). In males, important for ADAM2 processing as well as other acrosomal proteins with roles in fertilization and critical for normal fertilization events such as sperm capacitation, acrosome reaction and binding of sperm to zona pellucida (By similarity). Plays also a role in female fertility, involved in the regulation of trophoblast migration and placental development, may be through the proteolytical processing and activation of proteins such as IGF2 (PubMed:16040806). May also participate in folliculogenesis in the ovaries (By similarity).
Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases implicated in tumor invasion and metastasis, must undergo zymogen activation prior to expressing any proteolytic activity. Although the cysteine-switch model predicts the well-established autoactivation process, approximately 40% of the known MMPs possess a conserved RXKR motif between their pro- and catalytic domains and, thus, could be activated directly by members of the proprotein convertase family. To further understand this process, we analyzed the activation of proMT3-MMP as a model system. We demonstrated that the conversion of MT3-MMP zymogen into active form is dependent on both the furin-type convertase activity and the R(116)RKR motif. Consistently, MT3-MMP was colocalized with furin in the trans-Golgi network by confocal microscopy. However, neither furin activity nor its recognition site in MT3-MMP is required for the observed colocalization. In fact, the colocalization pattern remains intact, even in the presence
Proteolysis of Precursor proteins regulates many cellular processes like gene expression, embryogenesis, cell cycle, programmed cell death, intracellular protein targeting and endocrine/neural functions. All these processes needs proteolytic cleavage of the precursor protein and in this context this can be done by serine proteases in the secretory pathway. These proteases are calcium dependent serine endoproteases and are related to yeast and subtilisin proteases and therefore called Subtilisin-like Proprotein Convertases (SPCs) or PCs. Till now they identified & characterized seven members of this family in mammals and they have conserved signal peptides, pro-regions, catalytic and P-domains but they differ in C-terminal domains. These proteases get activated by autocatalytic cleavage of an N-terminal propeptide just like Subtilisin which is required for folding and activity. Studies predict that an eight-stranded beta barrel is formed due to folding of the P domain which interacts through a ...
Glioblastoma is the most common and aggressive intrinsic brain tumor in adults. Self-renewing, highly tumorigenic glioma-initiating cells (GIC) have been linked to glioma invasive properties, immunomodulation, and increased angiogenesis, leading to resistance to therapy. TGF-β signaling has been associated with the tumorigenic activity of GIC. TGF-β is synthesized as a precursor molecule and proteolytically processed to the mature form by members of the family of the proprotein convertases subtilisin/kexin. In this study we report that furin is unique among the proprotein convertases subtilisin/kexin in being highly expressed in human GIC. Furin cleaves and promotes activation of pro-TGF-β1 and pro-TGF-β2, and TGF-β2 in turn increases furin levels. Notably, TGF-β2 controls furin activity in an ALK-5-dependent manner involving the ERK/MAPK pathway. We thus uncover a role of ERK1 in the regulation of furin activity by supporting a self-sustaining loop for high TGF-β activity in GIC. ...
Although cardiovascular disease has been decreasing for decades, it remains the leading cause of death in the United States. Further progress will require both optimal application of proven approaches and the development of new ways to prevent and treat atherosclerosis. Inhibitors of proprotein convertase subtilisin/kexin 9 (PCSK9), which substantially reduce cholesterol levels, are an exciting new approach based on insights from genetics and rational drug development (1). However, the U.S. Food and Drug Administration-approved PCSK9 monoclonal antibodies, alirocumab (2) and evolocumab (3), came to market priced at $14 000 per year-more than 100 times the cost of a generic statin. An ounce of prevention might be worth a pound of cure, but how much is a pound of prevention worth ...
The conclusion that pro-ςE is associated with the cytoplasmic membrane and that this membrane association depends on the pro-amino acid sequence was independently reached in the concurrent investigation of Zhang et al. (37), who carried out subcellular fractionation experiments. That the pro-amino acid sequence also causes pro-ςE to become sequestered at the asymmetrically positioned septum is consistent with the previously reported observations of Ju et al. (6) who found that the NH2-terminal 55 amino acids of pro-ςE are sufficient to cause a fusion to GFP to become septum associated. Our present results confirm and extend the findings of Ju et al. by showing that pro-ςE is initially associated with the cytoplasmic membrane of the predivisional sporangium and that the nonrecombinant, native form of the proprotein becomes concentrated at the septum of the postdivisional sporangium.. In a parallel study on the properties of the prosequence of the late-stage mother cell-specific transcription ...
Neuroendocrine Secretory Protein 7B2: An acidic protein found in the NEUROENDOCRINE SYSTEM that functions as a molecular chaperone for PROPROTEIN CONVERTASE 2.
Vg convertase: subtilisin-like enzyme which cleaves pro-vitellogenin in fat bodies; isolated from the mosquito A. aegypti; amino acid sequence in first source; GenBank L46373
The structure of the precursor of the muscle mass regulator myostatin/GDF8 shows an open‐armed conformation, similar to pro‐activin A and distinct from pro‐TGF‐β1. An enhanced interface between prodomains and the mature growth factor allows pro‐myostatin to persist as a latent, antagonist resistant complex even after processing of the precursor by furin‐like proteases.. ...
Using a retinoic acid deficiency-induced squamous metaplasia model of HNECs, we observed a significant increase in the expression of PC5/6A, a PC member, and BMP-2, a candidate substrate for PC5/6A. Specific lentiviral shRNA-mediated PC5/6A knockdown decreased BMP-2 expression and maturation, decreased expression of squamous cell markers, and increased expression of ciliated cell markers. Dec-RVKR-CMK, a PC inhibitor, and LDN-193189, a BMP receptor inhibitor, suppressed squamous differentiation, promoted mucociliary differentiation, and down-regulated the BMP-2/Smad1/5/8/p38 signalling pathways. Dec-RVKR-CMK also decreased expression of PC5/6A, but not furin, another PC member, suggesting the involvement of PC5/6A in squamous differentiation of HNECs. Overexpression of PC5/6A and BMP-2 in the human nasal epithelial cell line RPMI-2650 demonstrated that PC5/6A can activate BMP-2. Under retinoic acid-sufficient culture conditions for mucociliary differentiation of HNECs, short-term expression of ...
Furin, a subtilisin/kesin-like proprotein convertase (PC), activates membrane-bound MT1-MMP, which facilitates pro-gelatinase A (MMP2). These activated MT1-MMP and MMP2 are involved in cancer cell invasion and metastasis. In this study, we investigate the contribution of MMP2 activated by furin to cellular invasiveness of cumulatively irradiated cells.. Using previously established AMC-HN3 and AMC-HN8 cell line from laryngeal carcinoma patient, we have generated isogenic model of cumulatively irradiated AMC-HN3R and AMC-HN8R cell line, respectively. AMC-HN3R cells were increased furin expression with upregulation of MT1-MMP/MMP2 and their invasiveness by two fold (p , 0.05) compared to AMC-HN3, while AMC-HN8R cells had no differences compared to AMC-HN8. In case of AMC-HN3R, inhibition of furin activity with the synthetic inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl-keton, CMK, showed a significant decrease of MT1-MMP/MMP2 and in vitro cellular invasiveness. Tumors obtained after subcutaneous ...
The results above define the location of the cleavage site in QSOX1A as occurring between the peptide sequence used to raise the anti-QSOX1A antibody and the TM domain (Figure 5A). To identify potential proteases responsible for the cleavage of QSOX1A, we first searched the UniProt database [26] for all proteases that are known to be present within the human ER and Golgi apparatus (Supplementary Table S1 at http://www.biochemj.org/bj/454/bj4540181add.htm). The resulting list of proteases was analysed manually with regard to their substrate specificities and consensus cleavage patterns. Three of the PPCs (proprotein convertases), PCSK3, PCSK6 and PCSK7, particularly stood out as they cleave at dibasic motifs, two of which are present in the QSOX1A amino acid sequence. The QSOX1A amino acid sequence also was analysed for potential cleavage sites using the ProP 1.0 Server [27]. Two of the predicted PPC cleavage sites are present in the region of interest with cleavage occurring C-terminally of ...
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] This gene encodes a type-I receptor transmembrane protein that is a member of the vacuolar protein sorting 10 receptor family. Proteins of this family are defined by a vacuolar protein sorting 10 domain at the N-terminus. The N-terminal segment of this domain has a consensus motif for proprotein convertase processing, and the C-terminal segment of this domain is characterized by ten conserved cysteine residues. The vacuolar protein sorting 10 domain is followed by a leucine-rich segment, a transmembrane domain, and a short C-terminal cytoplasmic domain that interacts with adaptor molecules. The transcript is expressed at high levels in the brain, and candidate gene studies suggest that genetic variation in this gene is associated with Alzheimer's disease. Consistent with this observation, knockdown of the gene in cell culture results in an increase in amyloid precursor protein processing. ...
Introduction: Anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies have been very effective to lower low-density lipoprotein (LDL)-cholesterol. They attracted the attention on PCSK9 enzyme role in multiple pathways and underlined the complex correlations between lipid metabolism and various other liver or extrahepatic diseases, that are insufficiently known. Hepatocyte nuclear factor 1, sterol regulatory element-binding protein (SREBP) 1c and SREBP2 are the main modulators of liver PCSK9 gene and protein expression, processes that can also be influenced by some natural and synthetic compounds (as berberine, or bortezomib and rosuvastatin, respectively), endoplasmic reticulum stress, metabolic status and the diurnal pattern.. Aim: This minireview is an analysis of PCSK9 involvement in liver pathology.. Results and Conclusion: PCSK9 is a key enzyme which increases LDL-receptor degradation. Hepatitis C virus (HCV) enters into hepatocytes in combination with lipoproteins through ...
Methods and Results-Patients with heterozygous familial hypercholesterolemia diagnosed by Simon Broome criteria with LDL-C ≥2.6 mmol/L (100 mg/dL) despite statin therapy with or without ezetimibe were randomized 1:1:1 to AMG 145 350 mg, AMG 145 420 mg, or placebo-administered subcutaneously every 4 weeks. The primary end point was percentage change from baseline in LDL-C at week 12. Of 168 patients randomized, 167 received investigational product and were included in the full analysis set (mean [SD] age, 50 [13] years; 47% female; 89% white; mean [SD] baseline LDL-C, 4.0 [1.1] mmol/L (156 [42] mg/dL)). At week 12, LDL-C reduction measured by preparative ultracentrifugation (least squares mean [standard error (SE)]) was 43 (3)% and 55 (3)% with AMG 145 350 mg and 420 mg, respectively, compared with 1 (3)% increase with placebo (P,0.001 for both dose groups). Serious adverse events (not considered treatment-related) occurred in 2 patients on AMG 145. ...
A recent study has shown that Cr-1 controls processing of the Nodal proprotein by recruiting proprotein convertases such as furin or PACE4 (Blanchet et al., 2008). Because processing by furin-like convertases (S1 cleavage) is also a prerequisite to generate mature heterodimerized Notch receptors (Logeat et al., 1998), we hypothesized that CR-1 may affect this processing step. Similar to the sequestration of the Nodal precursor protein into lipid rafts (Blanchet et al., 2008), forced expression of CR-1 in CR-1-deficient CHO cells enhanced the localization of the FL Notch1 protein in the lipid raft fraction in which glycosylphosphatidylinositol-anchored proteins such as CR-1 are enriched (Fig. 4 B). Furthermore, we assessed the effect of CR-1 expression on S1 cleavage of Notch1 in the presence of the γ-secretase inhibitor DAPT to exclude the effect on ligand-induced S3 cleavage (Fig. 4, C and D). CR-1 expression caused a dose-dependent increase in enhancement of the cleaved form of Notch1. This ...
AIMS: Individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia represent a high-risk and difficult-to-treat population. ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) compared alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with T2DM and mixed dyslipidaemia not optimally managed by maximally-tolerated statins. MATERIALS AND METHODS: UC options (no additional lipid-lowering therapy; fenofibrate; ezetimibe; omega-3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open-label alirocumab 75 mg every 2 weeks (Q2W; with increase to 150 mg Q2W at Week [W]12 if W8 non-high-density lipoprotein cholesterol [non-HDL-C] was ≥2 ...
The three distinct activation pathways of complement converge with the formation of a C5 convertase. The cleavage of C5 by this convertase initiates…
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Success of current therapies is still limited and outcome is particularly poor for metastatic alveolar rhabdomyosarcoma (aRMS). We previously identified the proprotein convertase furin as potential target for specific drug delivery with RMS-homing peptides. Furin is a protease that converts inactive precursor proteins into bioactive proteins and peptides. In this study, we investigate the biological role of furin in aRMS progression in vitro and in vivo. Furin expression was confirmed in over 86% RMS biopsies in a tissue microarray (n=89). Inducible furin silencing in vitro led to significant impairment of cell viability and proliferation in all investigated aRMS cell lines, but not in MRC5 fibroblasts. Furthermore, the aRMS cell lines Rh3 and Rh4 revealed to be very sensitive to furin silencing, undergoing caspase-dependent cell death. Notably, furin silencing in vivo led to complete remission of established Rh4 tumors ...
E-cadherin is synthesized as a precursor and then undergoes cleavage by proprotein convertases. This processing is essential for E-cadherin maturation and cell adhesion. Loss of cell adhesion causes detachment-induced apoptosis- anoikis. Anoikis can be inhibited despite loss of cell-matrix interactions by preserving E-cadherin mediated cell-cell adhesion. Conversely, acute loss of E-cadherin sensitizes cells to apoptosis by unknown post-translational mechanisms. In response to drug treatment of breast cancer cells, our analysis revealed that two independent modifications of E-cadherin inhibit its cell surface transport. Firstly, O-linked beta-N-acetylglucosamine (O-GlcNAc) modification of the cytoplasmic domain retains E-cadherin in the endoplasmic reticulum. Secondly, incomplete processing by proprotein convertases arrests E-cadherin transport late in the secretory pathway. We demonstrated these E-cadherin modifications (detected by specific lectins and antibodies) do not affect binding to ...
Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is a protein that prevents low-density lipoprotein (LDL) clearance from plasma through degradation of low-density lipoprotein receptors (LDL-R). Mutations that up- or down-regulate PCSK9 have been shown to affect risk of cardiovascular disease independently of plasma LDL level. In light of these discoveries, plasma PCSK9 level may prove useful as a biomarker for cardiovascular risk. Methods: An exhaustive search of the available medical literature was performed using the MEDLINE (Ovid), CINAHL and Web of Science databases. Keywords included PCSK9, evolocumab, alirocumab, myocardial infarction, cardiovascular disease and coronary artery disease (CAD). Inclusion criteria consisted of studies published in English that were performed on a human population, in the absence of statin therapy with endpoints including occurrence of a first cardiovascular event and severity of coronary artery stenosis. Results: Two studies met eligibility criteria for
PC1 and PC2 are subtilisin-like processing enzymes capable of cleaving thyrotropin releasing hormone (TRH) precursor (pro-TRH) at paired basic residues in vitro. In the paraventricular nucleus of the hypothalamus (PVN), pro-TRH is synthesized to control adenohypophysial thyrotropin and prolactin release. Biochemical and immunological approaches have shown that in the hypothalamus, pro-TRH is extensively cleaved at pairs of basic amino acids. We quantified, by two different approaches, in situ hybridization (ISH) on consecutive cryostat sections or double label ISH, the proportion of PVN TRH neurons containing either PC1 or PC2 mRNAs. Both techniques gave similar results: PC2 mRNA was present in 60-70% of TRH neurons, and PC1 mRNA in 37-46%. Values were similar in the anterior and medial parts of the parvocellular PVN. TRH neurons containing either PC1 or PC2 mRNA were found throughout the areas containing TRH cells without any evidence of anatomical segregation. These results suggest a biochemical
Proteolytic processing is required for the activation of numerous viral glycoproteins. Here we show that the envelope glycoprotein from the Zaire strain of Ebola virus (Ebo-GP) is proteolytically processed into two subunits, GP1 and GP2, that are likely covalently associated through a disulfide linkage. Murine leukemia virions pseudotyped with Ebo-GP contain almost exclusively processed glycoprotein, indicating that this is the mature form of Ebo-GP. Mutational analysis identified a dibasic motif, reminiscent of furin-like protease processing sites, as the Ebo-GP cleavage site. However, analysis of Ebo-GP processing in LoVo cells that lack the proprotein convertase furin demonstrated that furin is not required for processing of Ebo-GP. In sharp contrast to other viral systems, we found that an uncleaved mutant of Ebo-GP was able to mediate infection of various cell lines as efficiently as the wild-type, proteolytically cleaved glycoprotein, indicating that cleavage is not required for the ...
K08653 MBTPS1; membrane-bound transcription factor site-1 protease [EC:3.4.21.112] K01349 FURIN; furin [EC:3.4.21.75] K01359 PCSK1; proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] K01360 PCSK2; proprotein convertase subtilisin/kexin type 2 [EC:3.4.21.94] K08654 PCSK5; proprotein convertase subtilisin/kexin type 5 [EC:3.4.21.-] K08672 PCSK6; proprotein convertase subtilisin/kexin type 6 [EC:3.4.21.-] K08673 PCSK7; proprotein convertase subtilisin/kexin type 7 [EC:3.4.21.-] K13050 PCSK9; proprotein convertase subtilisin/kexin type 9 [EC:3.4.21.-] K01280 TPP2; tripeptidyl-peptidase II [EC:3.4.14.10 ...
... , Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
We examine the secondary preventive effect of acute phase use of PCSK9 inhibitors after coronary intervention in patients with acute myocardial infarction.
Reaktivität: Fledermaus, Huhn, Rind (Kuh) and more. 63 verschiedene PCSK2 Antikörper vergleichen. Alle direkt auf antikörper-online bestellbar!
sp:NEC1_MOUSE tr:Q32MU0_MOUSE] Pcsk1, Nec-1, Nec1, PC1, PC3, Phpp-1, SPC3; proprotein convertase subtilisin/kexin type 1; K01359 proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] ...
sp:NEC1_MOUSE] Pcsk1, Nec-1, Nec1, PC1, PC3, Phpp-1, SPC3; proprotein convertase subtilisin/kexin type 1; K01359 proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] ...
lcm:102356617 K01359 proprotein convertase subtilisin/kexin type 1 [EC:3.4.21.93] , (RefSeq) PCSK1; proprotein convertase subtilisin/kexin type 1 (A) MGARSRCVSSVVVALLAGLCTISLSNGEKQYVNEWAVEVPGGPRAANAIADELGYELMGQ IGSLDNHYLFRHKSHPRRSRRSANHFTKRLSDDERVTWAEQQYEKPRSKRSPARDCVDCL PEKMFNDPMWNQQWYLQDMRTSQLLPKLDLHVIPVWKKGITGKGVVITVLDDGLEWNHTD IYPNYDPEASYDFNNNDHDPFPRYDPTNENKHGTRCAGEIAMHANNNKCGVGVAYNSKVG GIRMLDGIVTDAIEASSIGFNPEHVDIYSASWGPNDDGKTVEGPGRLAQKAFEYGIQKGR GRKGSIFVWASGNGGRQGDNCDCDGYTDSIYTISISSASQQGLSPWYAEKCSSTLATAYS SGDYTDQRITSADLHNDCTGTHTGTSASAPLAAGIFALALEANPSLTWRDLQHLIVWTTE YDPLANNPGWKKNGAGLMVNSRFGFGLLNAKALVDLADPQTWKTVPEKKQCIVKDDSFEP RLLKADGEVIIEIPTKACEGQENNIKSLEHVQVEASIEYTRRGDLHITLTSPSGTTTVLL AERARDISPNGFKNWAFMSVHTWGEDPVGSWVLRITDVSGRLKNEGRIVSWKLILHGTST KPHHMKKLRVYTPYNTVQNDRRGVEKMADFEEDDTTTHESHAPKPTETATTKEGKEERAQ SEAMKHLLQNAFNRQTAQNRALEDMPKENLNIPLEKFYEALDKLNKHPQQKDSEDDLYND YSDLFYNVKPYRHRDDRLLQALFELLKKEN ...
A total of 406 participants were randomized to the AMG 145 treatment arms, placebo arms, and the ezetimibe arm, with approximately 45 participants per arm. The mean age of the patients was 51 years, 34% were men, and 79% were white. Mean LDL-C concentration at baseline was 3.7 mmol/L. Of the patients enrolled, 21% of patients had two or more cardiovascular risk factors, 32% had metabolic syndrome, and no one had a history of coronary artery disease. AMG 145 significantly reduced LDL-C concentrations in all dose groups. The changes from baseline were -41.0% (95% confidence interval -46.2 to -35.8) for the AMG 70 mg/2-week dose; -43.9% (-49.0 to -38.7) for the 105 mg/2-week dose; and -50.9% (-56.2 to -45.7) for the 140 mg/2-week dose. Doses given every 4 weeks also resulted in reduced LDL-C. The changes from baseline were -39.0% (-44.1 to -34.0) for the 280 mg/4-week dose; -43.2% (-48.3 to -38.1) for the 350 mg/4-week dose; and -48.0% (-53.1 to -42.9) for the 420 mg/4-week dose. The placebo groups ...
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Complete information for PCSK1N gene (Protein Coding), Proprotein Convertase Subtilisin/Kexin Type 1 Inhibitor, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Complete information for PCSK9 gene (Protein Coding), Proprotein Convertase Subtilisin/Kexin Type 9, including: function, proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium
Proprotein convertase furin is responsible for the processing of a wide variety of precursors consisted of signal peptide, propeptide and mature peptide in mammal. Many precursors processed by furin have important physiological functions and can be recombinantly expressed in Pichia pastoris expression system for research, pharmaceutical and vaccine applications. However, it is not clear whether the furin cleavage sites between the propeptide and mature peptide can be properly processed in P. pastoris, bringing uncertainty for proper expression of the coding DNA sequences of furin precursors containing the propeptides and mature peptides. In this study, we evaluated the ability of P. pastoris to process furin cleavage sites and how to improve the cleavage efficiencies of furin cleavage sites in P. pastoris. The results showed that P. pastoris can process furin cleavage sites but the cleavage efficiencies are not high. Arg residue at position P1 or P4 in furin cleavage sites significantly affect cleavage
MONDAY, Oct. 30, 2017 (HealthDay News) -- A combination of clinical factors and payer type increase the likelihood of approval for proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) treatment, and rates of approval are low overall, according to a study published online Oct. 30 in Circulation.. Gregory P. Hess, M.D., from the University of Pennsylvania in Philadelphia, and colleagues conducted a retrospective cohort study using nationwide pharmacy claims linked to electronic medical records. The data set included more than 220 million patients from all 50 states and all payer types, with 5,140 distinct health plans. In the pharmacy data set, PCSK9i prescriptions were submitted for 51,466 patients. Approval or rejection of PCSK9i prescription claims was the main outcome.. The researchers found that 47 percent of patients who were prescribed a PCSK9i were approved for coverage by the payer. Age ,65 years, history of atherosclerotic cardiovascular disease, prescription by a ...
Monoclonal antibody that binds to PCSK9 (proprotein convertase subtilisin/kexin type 9). LDL-C is cleared from the circulation preferentially through t
Sanofi and Regeneron hosted an IR Thematic Conference Call for the financial community focusing on alirocumab during the American College of Cardiology Annual Meeting.. Alirocumab (SAR236553/ REGN727) is an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) for the reduction of LDL-cholesterol. Alirocumab is currently being evaluated in a large Phase 3 program in patients with hypercholesterolemia. ...
Sanofi and Regeneron hosted an IR Thematic Conference Call for the financial community focusing on alirocumab during the European Society of Cardiology Congress in Barcelona.. Alirocumab (SAR236553/ REGN727) is an investigational monoclonal antibody targeting PCSK9 (proprotein convertase subtilisin/kexin type 9) for the reduction of LDL-cholesterol. Alirocumab is currently being evaluated in a large Phase 3 program in patients with hypercholesterolemia ...
Matthew Garrett PharmD candidate 2015, Mercer University College of Pharmacy Evolocumab is a human monoclonal antibody that is still in clinical trials. Previous clinical trials have shown that evolocumab along with diet and statins lowers patients LDL levels. Evolocumab is a proprotein convertase subtilisin/kexin type 9 inhibitor, which leads to more low-density lipoprotein (LDL) receptors…
PACE4 antibody (proprotein convertase subtilisin/kexin type 6) for IHC-P. Anti-PACE4 pAb (GTX39485) is tested in Human samples. 100% Ab-Assurance.
alpha-2-HS-glycoprotein (AHSG) also known as fetuin-A is a protein that in humans is encoded by the AHSG gene. Fetuin-A belongs to the fetuin class of plasma binding proteins and is more abundant in fetal than adult blood. Alpha2-HS glycoprotein, a glycoprotein present in the serum, is synthesized by hepatocytes. The AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a single mRNA. It is involved in several functions, such as endocytosis, brain development and the formation of bone tissue. The protein is commonly present in the cortical plate of the immature cerebral cortex and bone marrow hemopoietic matrix, and it has therefore been postulated that it participates in the development of the tissues. However, its exact significance is still obscure. The choroid plexus is an established extrahepatic expression site. The mature circulating AHSG molecule consists of two polypeptide chains, which are both cleaved from a proprotein encoded from a ...