A5009035456- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Growth Hormone and Insulin-like Growth Factors
- Cellular transport and secretion
- Regulation of Appetite and Obesity
- Peptidase Inhibition and Analysis
- Lipoproteins and Cardiovascular Health
- Endoplasmic Reticulum Stress and Disease
- Pancreatic function and diabetes
- Biochemical Analysis and Sensing Techniques
- Chemical Synthesis and Analysis
- Protease and Inhibitor Mechanisms
- Adipose Tissue and Metabolism
- Pituitary Gland Disorders and Treatments
- Hormonal Regulation and Hypertension
- Ubiquitin and proteasome pathways
- Stress Responses and Cortisol
- Hypothalamic control of reproductive hormones
- Biotin and Related Studies
- Neuroendocrine regulation and behavior
- Cancer, Hypoxia, and Metabolism
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Glycosylation and Glycoproteins Research
- Signaling Pathways in Disease
- Adipokines, Inflammation, and Metabolic Diseases
Montreal Clinical Research Institute
2014-2024
Université de Montréal
2000-2024
Ottawa Hospital Research Institute
2010-2020
Ottawa Hospital
2010-2020
University of Ottawa
2007-2018
University of Manitoba
2009
Dalhousie University
2008
Weatherford College
2008
Stem Cell Network
2006
Deutsches Herzzentrum der Charité
2002-2005
Seven secretory mammalian kexin-like subtilases have been identified that cleave a variety of precursor proteins at monobasic and dibasic residues. The recently characterized pyrolysin-like subtilase SKI-1 cleaves proproteins nonbasic In this work we describe the properties proteinase K-like subtilase, neural apoptosis-regulated convertase 1 (NARC-1), representing ninth member family. Biosynthetic microsequencing analyses WT mutant enzyme revealed human mouse pro-NARC-1 are autocatalytically...
The discovery of autosomal dominant hypercholesterolemic patients with mutations in the PCSK9 gene, encoding proprotein convertase NARC-1, resulting missense suggested a role low density lipoprotein (LDL) metabolism. We show that endoplasmic reticulum-localized proNARC-1 to NARC-1 zymogen conversion is Ca2+-independent and within autocatalytic processing site SSVFAQ↓SIP Val at P4 Pro P3′ are critical. S127R D374Y result ∼50–60% ≥98% decrease processing, respectively. In contrast, double...
A recombinant vaccinia virus vector was used to coexpress the two candidate mouse prohormone convertases, PC1 and PC2, together with proopiomelanocortin (POMC) in constitutively secreting cell line BSC-40 endocrine tissue-derived lines PC12 AtT-20, which exhibit regulated secretion. Monitoring of POMC processing demonstrated distinct cleavage specificities since analyzed (i) cleaves into corticotropin beta-lipotropin, (ii) PC2 beta-endorphin, an N-terminally extended containing joining...
Using a 796-basepair cDNA fragment obtained from mouse pituitary library we have screened two insulinoma libraries and isolated full-length clone (2516 basepairs; 753 amino acids), designated mPC1. The sequence of mPC1 codes for protein containing acids three potential N-glycosylation sites. This encodes putative novel subtilisin-like proteinase, exhibiting within its presumed catalytic domain 64%, 55%, 47% acid identity to the recently characterized candidate prohormone convertases human...
In order to define the enzymes responsible for maturation of precursors brain‐derived neurotrophic factor (proBDNF) and neurotrophin‐3 (proNT3), we have analysed their biosynthesis intracellular processing by proprotein convertases furin, PC1, PC2, PACE4, PC5 its isoform PC5/6‐B. these studies, utilized a vaccinia virus expression system in either BSC40 or furin activity‐deficient LoVo cells. Results demonstrated that both cells and, lesser extent, PACE4 PC5/6‐B effectively process proBDNF...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAmino acids of the Torpedo marmorata acetylcholine receptor .alpha. subunit labeled by a photoaffinity ligand for binding siteMichael Dennis, Jerome Giraudat, Florence Kotzyba-Hibert, Maurice Goeldner, Christian Hirth, Jui Yoa Chang, Claude Lazure, Michel Chretien, and Jean Pierre ChangeuxCite this: Biochemistry 1988, 27, 7, 2346–2357Publication Date (Print):April 5, 1988Publication History Published online1 May 2002Published inissue 5 April...
Processing of the β-amyloid precursor protein (βAPP) by β- and γ-secretases generates amyloidogenic peptide Aβ, a major factor in etiology Alzheimer's disease. Following recent identification β-secretase β-amyloid-converting enzyme (BACE), we herein investigate its zymogen processing, molecular properties, cellular trafficking. Our data show that among proprotein convertase family members, furin is converting pro-BACE into BACE within trans-Golgi network HK293 cells. While demonstrate...
In order to define the enzymes responsible for maturation of precursor nerve growth factor (proNGF), its biosynthesis and intracellular processing by pro-protein convertases furin, PC1, PC2, PACE4, PC5 isoform PC5/6-B were analysed using vaccinia virus expression system in cells containing a regulated and/or constitutive secretory pathway. Results demonstrate that both cell types lesser extent PACE4 PC5/6-B, are best candidate proNGF convertases. Furthermore, two processed NGF forms 16.5...
Using reverse transcriptase–PCR and degenerate oligonucleotides derived from the active-site residues of subtilisin/kexin-like serine proteinases, we have identified a highly conserved phylogenetically ancestral human, rat, mouse type I membrane-bound proteinase called subtilisin/kexin-isozyme-1 (SKI-1). Computer databank searches reveal that human SKI-1 was cloned previously but with no function. In situ hybridization demonstrates mRNA is present in most tissues cells. Cleavage specificity...
PC1 and PC2 are enzymes involved in the activation of prohormones via cleavage pairs basic amino acids. The expression levels each these were evaluated rat anterior neurointermediate pituitary lobes by situ hybridization Northern gel analysis after various pharmacological manipulations. All intermediate lobe melanotrophs expressed high mRNA lower mRNA. was highly throughout lobe; however, appreciable also found. Based on colocalization studies, corticotrophs found to express mRNA, but very...
Posttranslational processing of proproteins and prohormones is an essential step in the formation bioactive peptides, which particular importance nervous system. Following a long search for enzymes responsible protein precursor cleavage, family Kexin/subtilisin-like convertases known as PC1, PC2, furin have recently been characterized mammalian species. Their presence endocrine neuroendocrine tissues has demonstrated. This study examines mRNA distribution these rat CNS compares their...
By using reverse transcription-coupled PCR on rat anterior pituitary RNA, we isolated a 285-bp cDNA coding for novel subtilisin/kexin-like protein convertase (PC), called (r) PC7. screening spleen and PC12 cell lambda gt11 libraries, obtained composite 3.5-kb full-length sequence of rPC7. The open reading frame codes prepro-PC with 36-amino acid signal peptide, 104-amino prosegment ending cleavable RAKR sequence, 747-amino type I membrane-bound glycoprotein, representing the mature form this...
By using reverse transcriptase/PCR and oligonucleotide sequences derived from conserved segments (including the RRGDL sequence) of known proprotein convertases (PCs) PC1, PC2, furin, PC4, we identified a subtilisin/kexin-like PC called PC5 in both mouse rat tissues. The composite structure (2.85 kb) was deduced analysis transcription/PCR products combined with sequence clone isolated cDNA library made corticotropin-activated adrenocortical Y1 cells. structures showed that closest homologue...
Identification of the β-lipotropic hormone (β-LPH)-producing cells in several species, including man, was performed with technique involving use unlabeled antibody and peroxidase- antiperoxidase complex. Serial paraffin ultrathin sections were treated for detection both β-LPH ACTH at light electron microscopic levels. It clearly shown that could be found only corticotropic located pars intermedia distalis all species studied. At microscope level, it established is contained secretory...
A substance called atrial natriuretic factor (ANF), localized in secretory granules of cardiocytes, was isolated as four homologous peptides from homogenates rat atria. The complete sequence the longest form showed that it is composed 33 amino acids. three other shorter forms (2-33, 3-33, and 8-33) represent amino-terminally truncated versions acid parent molecule shown by analysis sequence, composition, or both. proposed primary structure agrees entirely with composition reveals no...
Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein (LDLC) negatively regulating receptor (LDLR) levels. PCSK9 variants result in 'gain function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has documented individuals who carry 'loss variants. circulates human plasma, and we...
The rat cDNA sequence of PC4 (rPC4), representing a new member the Kex2/subtilisin-like proprotein convertases, demonstrated presence at least three rPC4 mRNAs resulting in production rPC4-A (654 amino acids), rPC4-B (619 and rPC4-C (609 acids) with different C-terminal sequences. Analogous to PC4, cDNAs were also found for mouse PC4. observed molecular diversity mRNA possibly results from differential splicing and/or exon skipping parent gene. mRNA, major form 2.8 kilobases, was highly...