ArticleMolecular biology of the cell2005
The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 94 citations in OpenAlex.
- Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif.Reviews in medical virology · 2025Review
- The proprotein convertase BLI-4 promotes collagen secretion prior to assembly of the Caenorhabditis elegans cuticle.PLoS genetics · 2023Article
- The proprotein convertase BLI-4 promotes collagen secretion during assembly of thebioRxiv : the preprint server for biology · 2023Article
- PCSK6 and Survival in Idiopathic Pulmonary Fibrosis.American journal of respiratory and critical care medicine · 2023Article
- Proprotein Convertase Subtilisin/Kexin 6 in Cardiovascular Biology and Disease.International journal of molecular sciences · 2022Review
- Remodeling of the Lamina Cribrosa: Mechanisms and Potential Therapeutic Approaches for Glaucoma.International journal of molecular sciences · 2022Review
- Proprotein Convertases and the Complement System.Frontiers in immunology · 2022Review
- Matrix Metalloproteinases in Human Decidualized Endometrial Stromal Cells.Current issues in molecular biology · 2021Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Molecular evolution of PCSK family: Analysis of natural selection rate and gene loss.PloS one · 2021Article
- Biology of Tissue Inhibitor of Metalloproteinase 3 (TIMP3), and Its Therapeutic Implications in Cardiovascular Pathology.Frontiers in physiology · 2020Review
- Evaluation of PACE4 isoforms as biomarkers in thyroid cancer.Journal of otolaryngology - head & neck surgery = Le Journal d'oto-rhino-laryngologie et de chirurgie cervico-faciale · 2018Article
- Functional analysis of corin protein domains required for PCSK6-mediated activation.The international journal of biochemistry & cell biology · 2018Article
- PACE4 (PCSK6): another proprotein convertase link to iron homeostasis?Haematologica · 2015Article
- The paired basic amino acid-cleaving enzyme 4 (PACE4) is involved in the maturation of insulin receptor isoform B: an opportunity to reduce the specific insulin receptor-dependent effects of insulin-like growth factor 2 (IGF2).The Journal of biological chemistry · 2015Article
- PACE4-based molecular targeting of prostate cancer using an engineered ⁶⁴Cu-radiolabeled peptide inhibitor.Neoplasia (New York, N.Y.) · 2014Article
- Article
- The Multi-Leu peptide inhibitor discriminates between PACE4 and furin and exhibits antiproliferative effects on prostate cancer cells.Journal of medicinal chemistry · 2012Article
- Opposite roles of furin and PC5A in N-cadherin processing.Neoplasia (New York, N.Y.) · 2012Article
- The biology and therapeutic targeting of the proprotein convertases.Nature reviews. Drug discovery · 2012Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proprotein convertases PC5, PACE4 and furin contain a C-terminal cysteine-rich domain (CRD) of unknown function. We demonstrate that the CRD confers to PC5A and PACE4 properties to bind tissue inhibitors of metalloproteinases (TIMPs) and the cell surface. Confocal microscopy and biochemical analyses revealed that the CRD is essential for cell surface tethering of PC5A and PACE4 and that it colocalizes and coimmunoprecipitates with the full-length and C-terminal domain of TIMP-2. Surface-bound PC5A in TIMP-2 null fibroblasts was only observed upon coexpression with TIMP-2. In COS-1 cells, plasma membrane-associated PC5A can be displaced by heparin, suramin, or heparinases I and III and by competition with excess exogenous TIMP-2. Furthermore, PC5A and TIMP-2 are shown to be colocalized over the surface of enterocytes in the mouse duodenum and jejunum, as well as in liver sinusoids. In conclusion, the CRD of PC5A and PACE4 functions as a cell surface anchor favoring the processing of their cognate surface-anchored substrates, including endothelial lipase.
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