ArticleThe Journal of biological chemistry2010
Osteopontin is cleaved at multiple sites close to its integrin-binding motifs in milk and is a novel substrate for plasmin and cathepsin D.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 119 citations in OpenAlex.
- Context-dependent roles of osteopontin in aging-related neurological disorders.The Journal of international medical research · 2026Review
- Metabolically and epigenetically reprogrammed splenic TRNP1Nature genetics · 2026Article
- Osteopontin in Atrial Fibrillation and Atrial Remodeling.Journal of the American Heart Association · 2026Review
- Developments in Ion Exchange Chromatography-Mass Spectrometry for the Characterization of Intact Proteins and Proteoforms.Journal of separation science · 2025Review
- An expert panel on the adequacy of safety data and physiological roles of dietary bovine osteopontin in infancy.Frontiers in nutrition · 2024Review
- The Multifaceted Role of Osteopontin in Prostate Pathologies.Biomedicines · 2023Review
- Fingerprinting of Proteases, Protease Inhibitors and Indigenous Peptides in Human Milk.Nutrients · 2023Article
- Analytical Ultracentrifugation-Calibrated Anion-Exchange Chromatography for Sensitive and Intact Determination of Osteopontin in Infant Formula and Dairy Products.Journal of agricultural and food chemistry · 2023Article
- Review
- Milk Osteopontin and Human Health.Nutrients · 2023Review
- Osteopontin (OPN)/SPP1: from its biochemistry to biological functions in the innate immune system and the central nervous system (CNS).International immunology · 2023Review
- The Role and Clinical Relevance of Osteopontin in Allergic Airway Diseases.Journal of clinical medicine · 2023Review
- Influence of a Physiologically Formed Blood Clot on Pre-Osteoblastic Cells Grown on a BMP-7-Coated Nanoporous Titanium Surface.Biomimetics (Basel, Switzerland) · 2023Article
- Naturally Occurring N-Terminal Fragments of Bovine Milk Osteopontin Are Transported across Models of the Intestinal Barrier.Biomedicines · 2023Article
- The Effect of Human and Bovine Milk Osteopontin on Intestinal Caco-2 Cells: A Transcriptome Comparison.Nutrients · 2023Article
- COVID-19 Molecular Pathophysiology: Acetylation of Repurposing Drugs.International journal of molecular sciences · 2022Review
- Effects of rmBMP-7 on Osteoblastic Cells Grown on a Nanostructured Titanium Surface.Biomimetics (Basel, Switzerland) · 2022Article
- Clinical and Molecular Implications of Osteopontin in Heart Failure.Current issues in molecular biology · 2022Review
- Safety of bovine milk osteopontin as a Novel food pursuant to Regulation (EU) 2015/2283.EFSA journal. European Food Safety Authority · 2022Article
- The unfavorable clinical outcome of COVID-19 in smokers is mediated by H3K4me3, H3K9me3 and H3K27me3 histone marks.Epigenomics · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteopontin (OPN) is a highly modified integrin-binding protein present in most tissues and body fluids where it has been implicated in numerous biological processes. A significant regulation of OPN function is mediated through phosphorylation and proteolytic processing. Proteolytic cleavage by thrombin and matrix metalloproteinases close to the integrin-binding Arg-Gly-Asp sequence modulates the function of OPN and its integrin binding properties. In this study, seven N-terminal OPN fragments originating from proteolytic cleavage have been characterized from human milk. Identification of the cleavage sites revealed that all fragments contained the Arg-Gly-Asp(145) sequence and were generated by cleavage of the Leu(151)-Arg(152), Arg(152)-Ser(153), Ser(153)-Lys(154), Lys(154)-Ser(155), Ser(155)-Lys(156), Lys(156)-Lys(157), or Phe(158)-Arg(159) peptide bonds. Six cleavages cannot be ascribed to thrombin or matrix metalloproteinase activity, whereas the cleavage at Arg(152)-Ser(153) matches thrombin specificity for OPN. The principal protease in milk, plasmin, hydrolyzed the same peptide bond as thrombin, but its main cleavage site was identified to be Lys(154)-Ser(155). Another endogenous milk protease, cathepsin D, cleaved the Leu(151)-Arg(152) bond. OPN fragments corresponding to plasmin activity were also identified in urine showing that plasmin cleavage of OPN is not restricted to milk. Plasmin, but not cathepsin D, cleavage of OPN increased cell adhesion mediated by the alpha(V)beta(3)- or alpha(5)beta(1)-integrins. Similar cellular adhesion was mediated by plasmin and thrombin-cleaved OPN showing that plasmin can be a potent regulator of OPN activity. These data show that OPN is highly susceptible to cleavage near its integrin-binding motifs, and the protein is a novel substrate for plasmin and cathepsin D.
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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.