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Esben Skipper Sørensen

Osteopontin is highly susceptible to cleavage in bovine milk and the proteolytic fragments bind the αVβ3-integrin receptor

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Site-specific and partial proteolysis of milk proteins can both alter and increase their biological activity. The milk protein osteopontin (OPN) is a highly phosphorylated integrin-binding molecule present in most tissues and body fluids. Osteopontin is a biological substrate for matrix metalloproteinases, thrombin, plasmin, and cathepsin D. These proteases cleave OPN at several positions near the integrin-binding sequence Arg-Gly-Asp138. This cleavage can either increase or reduce the ability of OPN to bind integrins and illustrates that small differences in the cleavage pattern can have a substantial effect on the functionality of OPN. Bovine milk OPN (bOPN) exists in both intact full-length and cleaved forms, and in this study, 6 N-terminal bOPN fragments originating from proteolytic cleavage were purified and characterized by mass spectrometry. These fragments were generated by cleavage at the Lys145-Ser146, Arg147-Ser148, Lys149-Lys150, Phe151-Arg152, Arg152-Arg153, and Arg153-Ser154 peptide bonds. The principal protease in milk, plasmin, appeared to cleave 3 of these sites. However, the major cleavage site was observed to be at the Phe151-Arg152 bond, which does not match the specificity of plasmin. The bOPN fragments were shown to interact with the integrin receptor αVβ3 as efficiently as the well-characterized and highly active OPN fragment Ile1-Arg152, generated by thrombin cleavage of human milk OPN. These data show that OPN in milk is highly susceptible to proteolytic cleavage in the region containing the integrin-binding motifs, and the generated fragments are highly capable of binding cells via the αVβ3-integrin
Original languageEnglish
JournalJournal of Dairy Science
Volume97
Issue1
Pages (from-to)136-146
Number of pages10
ISSN0022-0302
DOIs
Publication statusPublished - Jan 2014

    Research areas

  • osteopontin, proteolytic cleavage, integrin, cell binding

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