ArticleJournal of cell communication and signaling2015
The role of PAPP-A in the IGF system: location, location, location.
Article in Journal of cell communication and signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
109 citing papers in PubMed, 194 citations in OpenAlex.
- Netazepide Inhibits Expression of Pappalysin 2 in Type 1 Gastric Neuroendocrine Tumors.Cellular and molecular gastroenterology and hepatology · 2020Trial
- Pharmacokinetics of IGF-1 in PAPP-A2-Deficient Patients, Growth Response, and Effects on Glucose and Bone Density.The Journal of clinical endocrinology and metabolism · 2017Trial
- Stanniocalcin-1 and -2: The insulin-like growth factor system and beyond.Molecular biology reports · 2026Review
- Integrated First-Trimester Assessment of Placental Biomarkers, Metabolic Indices, and IGF-1/IGFBP-5 in Relation to Subsequent Gestational Diabetes Mellitus: A Prospective Cohort Study.Medicina (Kaunas, Lithuania) · 2026Article
- Unravelling the Impact of Diabetes on Insulin-like Growth Factor (IGF) Axis Signalling in Mesenchymal Stem Cells Isolated from the Bone of Knee Joints.Bioengineering (Basel, Switzerland) · 2026Article
- Size in small-for-gestational-age neonates correlates with insulin-like growth factor-binding protein proteolysis and insulin-like growth factor-I bioavailability.Journal of the Endocrine Society · 2026Article
- Sex-specific hormonal rescue of bone growth in PAPPA2-deficient mice : a role for cannabinoid receptors and STAT3.Bone & joint research · 2026Article
- High Expression of PAPP-A Predicts Poor Outcomes in Oestrogen Receptor-Positive Breast Cancer Patients.Cancer medicine · 2026Article
- Pan-Cancer Analysis ofBiology · 2026Article
- Intertwining of the IGF system and animal welfare.Scientific reports · 2026Article
- Characterization of PAPP-A Patterns in Chronic Rhinosinusitis.Journal of inflammation research · 2026Article
- The Promise of Exosomes in Cardiac Repair: When 'Best Things Come in Small Packages'.Journal of cellular and molecular medicine · 2025Review
- IGF Pathway Components as Potential Biomarkers in Gastric Cancer.International journal of molecular sciences · 2025Article
- Paracrine IGFBP3 spatially coordinates IGF signaling to induce myocardial regeneration in mice.Journal of molecular and cellular cardiology · 2025Article
- The genetic architecture of cervical length is shared with spontaneous preterm birth risk.Communications medicine · 2025Article
- Review
- Transcriptional Changes in Cumulus Cells During In Vitro Maturation of Human Oocytes.Molecular reproduction and development · 2025Article
- The Proteinase PAPP-A has Deep Evolutionary Roots Outside of the IGF System.Genome biology and evolution · 2025Article
- Sox10 is required for systemic initiation of bone mineralization.Development (Cambridge, England) · 2025Article
- The Molecular Biology of Placental Transport of Calcium to the Human Foetus.International journal of molecular sciences · 2025Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although discovered as a placental protein present abundantly in the circulation of pregnant women, pregnancy-associated plasma protein-A (PAPP-A) is widely expressed in multiple tissues. PAPP-A is a highly specific metalloproteinase binding tightly to glycosaminoglycans present on the surface of cells. By cleaving a subset of insulin-like growth factor binding proteins (IGFBPs), PAPP-A thus functions within tissues as a growth-promoting enzyme, releasing bioactive IGF in close proximity to the IGF receptor. IGFBP-4 is believed to be the principal PAPP-A substrate, and the focus in this review is on PAPP-A enzymatic activity and its role in the PAPP-A-IGFBP-4-IGF axis, which is subject to regulation at several different levels. These include e.g., transcriptional control, competing reactions potentially sequestering IGF from IGFBP-4 and hence antagonizing PAPP-A-mediated IGF activation, and proteolytic inhibition of PAPP-A. The latter may involve the protein stanniocalcin-2 (STC2), recently found to potently inhibit PAPP-A activity by forming a covalent complex with PAPP-A. PAPP-A or complex-bound variants may escape from pathological tissues into the circulation. It is emphasized that the potential use of PAPP-A as a diagnostic or predictive biomarker in nonpregnant individuals requires precise knowledge of analyte identity and assay specificity in addition to an appropriate material for standardization. Finally, PAPP-A may serve as a therapeutic target to indirectly inhibit IGF signaling in tissues where this is driven by increased PAPP-A activity. By taking advantage of the intricate interaction between PAPP-A and IGFBP-4, highly specific and selective inhibition of PAPP-A is possible.
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.