ArticleThe Journal of biological chemistry2015
Stanniocalcin-1 Potently Inhibits the Proteolytic Activity of the Metalloproteinase Pregnancy-associated Plasma Protein-A.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 123 citations in OpenAlex.
- Stanniocalcin-1 Hormone in Nonpreeclamptic and Preeclamptic Pregnancy: Clinical, Life-Style, and Genetic Modulators.The Journal of clinical endocrinology and metabolism · 2016Pooled it
- Stanniocalcin-1 and -2: The insulin-like growth factor system and beyond.Molecular biology reports · 2026Review
- STC1 promotes osteogenic differentiation and represses inflammation via inhibition of NF‑κB signaling in mesenchymal stromal cells.Molecular medicine reports · 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
- Intertwining of the IGF system and animal welfare.Scientific reports · 2026Article
- Cadherin-16 regulates acoustic sensory gating in zebrafish through endocrine signaling.PLoS biology · 2025Article
- The IGF System and Aging.Endocrine reviews · 2025Review
- The Proteinase PAPP-A has Deep Evolutionary Roots Outside of the IGF System.Genome biology and evolution · 2025Article
- Stc2a inhibits IGF-stimulated somatic growth in favor of organismal survival under hypoxic stress.Frontiers in endocrinology · 2025Article
- Exploring free pregnancy associated plasma protein a (fPAPP-A) as a biomarker in early pregnancy.Practical laboratory medicine · 2024Article
- Cadherin 16 promotes sensory gating via the endocrine corpuscles of Stannius.bioRxiv : the preprint server for biology · 2024Article
- The pro-atherogenic enzyme PAPP-A is active in eluates from human carotid and femoral atherosclerotic plaques.Atherosclerosis plus · 2024Article
- The metalloproteinase PAPP-A is required for IGF-dependent chondrocyte differentiation and organization.Scientific reports · 2024Article
- Stanniocalcin Protein Expression in Female Reproductive Organs: Literature Review and Public Cancer Database Analysis.Endocrinology · 2024Review
- Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments.Biology of sex differences · 2024Article
- Implication of Pappalysins and Stanniocalcins in the Bioavailability of IGF-I in Children With Type 1 Diabetes Mellitus.Journal of the Endocrine Society · 2024Article
- The role of pregnancy associated plasma protein-A in triple negative breast cancer: a promising target for achieving clinical benefits.Journal of biomedical science · 2024Review
- The IGF-PAPP-A-Stanniocalcin Axis in Serum and Ascites Associates with Prognosis in Patients with Ovarian Cancer.International journal of molecular sciences · 2024Article
- Pregnancy associated plasma protein-A2 (PAPP-A2) and stanniocalcin-2 (STC2) but not PAPP-A are associated with circulating total IGF-1 in a human adult population.Scientific reports · 2024Article
- Genetic and Pharmacological Inhibition of PAPP-A Reduces Bleomycin-Induced Pulmonary Fibrosis in Aged Mice via Reduced IGF Signaling.Aging biology · 2024Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stanniocalcin-1 (STC1) is a disulfide-bound homodimeric glycoprotein, first identified as a hypocalcemic hormone important for maintaining calcium homeostasis in teleost fish. STC1 was later found to be widely expressed in mammals, although it is not believed to function in systemic calcium regulation in these species. Several physiological functions of STC1 have been reported, although many molecular details are still lacking. We here demonstrate that STC1 is an inhibitor of the metzincin metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A), which modulates insulin-like growth factor (IGF) signaling through proteolytic cleavage of IGF-binding proteins (IGFBPs). STC1 potently (Ki = 68 pm) inhibits PAPP-A cleavage of IGFBP-4, and we show in a cell-based assay that STC1 effectively antagonizes PAPP-A-mediated type 1 IGF receptor (IGF1R) phosphorylation. It has recently been found that the homologous STC2 inhibits PAPP-A proteolytic activity, and that this depends on the formation of a covalent complex between the inhibitor and the proteinase, mediated by Cys-120 of STC2. We find that STC1 is unable to bind covalently to PAPP-A, in agreement with the absence of a corresponding cysteine residue. It rather binds to PAPP-A with high affinity (KD = 75 pm). We further demonstrate that both STC1 and STC2 show inhibitory activity toward PAPP-A2, but not selected serine proteinases and metalloproteinases. We therefore conclude that the STCs are proteinase inhibitors, probably restricted in specificity to the pappalysin family of metzincin metalloproteinases. Our data are the first to identify STC1 as a proteinase inhibitor, suggesting a previously unrecognized function of STC1 in the IGF system.
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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.