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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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Osteopontin is highly susceptible to cleavage in bovine milk and the proteolytic fragments bind the αVβ3-integrin receptor. / Christensen, Brian Søndergaard; Sørensen, Esben Skipper.

In: Journal of Dairy Science, Vol. 97, No. 1, 01.2014, p. 136-146.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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@article{91215af9b2524fdf9c71d52b3d532638,
title = "Osteopontin is highly susceptible to cleavage in bovine milk and the proteolytic fragments bind the αVβ3-integrin receptor",
abstract = "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",
keywords = "osteopontin, proteolytic cleavage, integrin, cell binding",
author = "Christensen, {Brian S{\o}ndergaard} and S{\o}rensen, {Esben Skipper}",
year = "2014",
month = "1",
doi = "10.3168/jds.2013-7223",
language = "English",
volume = "97",
pages = "136--146",
journal = "Journal of Dairy Science",
issn = "0022-0302",
publisher = "Elsevier Inc",
number = "1",

}

RIS

TY - JOUR

T1 - Osteopontin is highly susceptible to cleavage in bovine milk and the proteolytic fragments bind the αVβ3-integrin receptor

AU - Christensen, Brian Søndergaard

AU - Sørensen, Esben Skipper

PY - 2014/1

Y1 - 2014/1

N2 - 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

AB - 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

KW - osteopontin

KW - proteolytic cleavage

KW - integrin

KW - cell binding

U2 - 10.3168/jds.2013-7223

DO - 10.3168/jds.2013-7223

M3 - Journal article

VL - 97

SP - 136

EP - 146

JO - Journal of Dairy Science

JF - Journal of Dairy Science

SN - 0022-0302

IS - 1

ER -