ArticleThe Journal of biological chemistry2015
Stanniocalcin-2 inhibits mammalian growth by proteolytic inhibition of the insulin-like growth factor axis.
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 87 papers.
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Who cites it
87 citing papers in PubMed, 184 citations in OpenAlex.
- Stanniocalcin-1 and -2: The insulin-like growth factor system and beyond.Molecular biology reports · 2026Review
- Paracrine IGFBP3 spatially coordinates IGF signaling to induce myocardial regeneration in mice.Journal of molecular and cellular cardiology · 2025Article
- Signatures of selection detected from whole-genome sequencing indicate that the small body size in dwarf rabbit breeds is caused by polygenic effects with a few major loci.Animal genetics · 2025Article
- LCORL and STC2 Variants Increase Body Size and Growth Rate in Cattle and Other Animals.Genomics, proteomics & bioinformatics · 2025Article
- 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
- Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress.Cell death & disease · 2024Article
- 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
- Stanniocalcin 2 governs cancer cell adaptation to nutrient insufficiency through alleviation of oxidative stress.Research square · 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
- Article
27 more citing papers are in PubMed but not listed here.
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
Mammalian stanniocalcin-2 (STC2) is a secreted polypeptide widely expressed in developing and adult tissues. However, although transgenic expression in mice is known to cause severe dwarfism, and targeted deletion of STC2 causes increased postnatal growth, its precise biological role is still unknown. We found that STC2 potently inhibits the proteolytic activity of the growth-promoting metalloproteinase, pregnancy-associated plasma protein-A (PAPP-A). Proteolytic inhibition requires covalent binding of STC2 to PAPP-A and is mediated by a disulfide bond, which involves Cys-120 of STC2. Binding of STC2 prevents PAPP-A cleavage of insulin-like growth factor-binding protein (IGFBP)-4 and hence release within tissues of bioactive IGF, required for normal growth. Concordantly, we show that STC2 efficiently inhibits PAPP-A-mediated IGF receptor signaling in vitro and that transgenic mice expressing a mutated variant of STC2, STC2(C120A), which is unable to inhibit PAPP-A, grow like wild-type mice. Our work identifies STC2 as a novel proteinase inhibitor and a previously unrecognized extracellular component of the IGF system.
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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.