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Carsten Scavenius

FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin

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FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin. / Schytte, Gitte N; Christensen, Brian; Bregenov, Ida; Kjøge, Katarzyna; Scavenius, Carsten; Petersen, Steen V; Enghild, Jan J; Sørensen, Esben S.

In: Journal of Cellular Biochemistry, Vol. 121, No. 12, 12.2020, p. 4809-4818.

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@article{28a2c03368854ca6b845a91d5fc30745,
title = "FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin",
abstract = "Osteopontin (OPN) is a ubiquitously expressed, multifunctional, and highly phosphorylated protein. OPN contains two neighboring integrin-binding motifs, RGD and SVVYGLR, which mediate interaction with cells. Phosphorylation and proteolytic processing affect the integrin-binding activities of OPN. Here we report that the kinase, FAM20C, phosphorylates Ser146 in the 143 RGDSVVYGLR152 motif of OPN and that Ser146 is phosphorylated in vivo in human and bovine milk. Ser146 is located right next to the RGD motif and close by the regulatory thrombin and plasmin cleavage sites in the OPN sequence. Phosphorylation of Ser146 could potentially affect the proteolytic processing and the integrin-binding activities of OPN. We show that phosphorylation of Ser146 does not affect the susceptibility of OPN for thrombin or plasmin cleavage. However, phosphorylation of Ser146 significantly reduces the RGD-mediated interaction with the αv β3 integrin in MDA-MB-435 and Moαv cells. This suggests a new mechanism by which specific phosphorylation of OPN can regulate interaction with the αv β3 integrin and thereby affect OPN-cell interaction.",
keywords = "APPARATUS CASEIN KINASE, BINDING, FAM20C, FRAGMENT, GLYCOSYLATION, GROWTH, IDENTIFICATION, MILK, POSTTRANSLATIONAL MODIFICATIONS, SEQUENCE, SITES, alpha(v)beta(3) integrin, osteopontin, phosphorylation, α β integrin",
author = "Schytte, {Gitte N} and Brian Christensen and Ida Bregenov and Katarzyna Kj{\o}ge and Carsten Scavenius and Petersen, {Steen V} and Enghild, {Jan J} and S{\o}rensen, {Esben S}",
note = "{\textcopyright} 2020 Wiley Periodicals, Inc.",
year = "2020",
month = dec,
doi = "10.1002/jcb.29708",
language = "English",
volume = "121",
pages = "4809--4818",
journal = "Journal of Cellular Biochemistry. Supplement",
issn = "0733-1959",
publisher = "JohnWiley & Sons, Inc.",
number = "12",

}

RIS

TY - JOUR

T1 - FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin

AU - Schytte, Gitte N

AU - Christensen, Brian

AU - Bregenov, Ida

AU - Kjøge, Katarzyna

AU - Scavenius, Carsten

AU - Petersen, Steen V

AU - Enghild, Jan J

AU - Sørensen, Esben S

N1 - © 2020 Wiley Periodicals, Inc.

PY - 2020/12

Y1 - 2020/12

N2 - Osteopontin (OPN) is a ubiquitously expressed, multifunctional, and highly phosphorylated protein. OPN contains two neighboring integrin-binding motifs, RGD and SVVYGLR, which mediate interaction with cells. Phosphorylation and proteolytic processing affect the integrin-binding activities of OPN. Here we report that the kinase, FAM20C, phosphorylates Ser146 in the 143 RGDSVVYGLR152 motif of OPN and that Ser146 is phosphorylated in vivo in human and bovine milk. Ser146 is located right next to the RGD motif and close by the regulatory thrombin and plasmin cleavage sites in the OPN sequence. Phosphorylation of Ser146 could potentially affect the proteolytic processing and the integrin-binding activities of OPN. We show that phosphorylation of Ser146 does not affect the susceptibility of OPN for thrombin or plasmin cleavage. However, phosphorylation of Ser146 significantly reduces the RGD-mediated interaction with the αv β3 integrin in MDA-MB-435 and Moαv cells. This suggests a new mechanism by which specific phosphorylation of OPN can regulate interaction with the αv β3 integrin and thereby affect OPN-cell interaction.

AB - Osteopontin (OPN) is a ubiquitously expressed, multifunctional, and highly phosphorylated protein. OPN contains two neighboring integrin-binding motifs, RGD and SVVYGLR, which mediate interaction with cells. Phosphorylation and proteolytic processing affect the integrin-binding activities of OPN. Here we report that the kinase, FAM20C, phosphorylates Ser146 in the 143 RGDSVVYGLR152 motif of OPN and that Ser146 is phosphorylated in vivo in human and bovine milk. Ser146 is located right next to the RGD motif and close by the regulatory thrombin and plasmin cleavage sites in the OPN sequence. Phosphorylation of Ser146 could potentially affect the proteolytic processing and the integrin-binding activities of OPN. We show that phosphorylation of Ser146 does not affect the susceptibility of OPN for thrombin or plasmin cleavage. However, phosphorylation of Ser146 significantly reduces the RGD-mediated interaction with the αv β3 integrin in MDA-MB-435 and Moαv cells. This suggests a new mechanism by which specific phosphorylation of OPN can regulate interaction with the αv β3 integrin and thereby affect OPN-cell interaction.

KW - APPARATUS CASEIN KINASE

KW - BINDING

KW - FAM20C

KW - FRAGMENT

KW - GLYCOSYLATION

KW - GROWTH

KW - IDENTIFICATION

KW - MILK

KW - POSTTRANSLATIONAL MODIFICATIONS

KW - SEQUENCE

KW - SITES

KW - alpha(v)beta(3) integrin

KW - osteopontin

KW - phosphorylation

KW - α β integrin

U2 - 10.1002/jcb.29708

DO - 10.1002/jcb.29708

M3 - Journal article

C2 - 32115754

VL - 121

SP - 4809

EP - 4818

JO - Journal of Cellular Biochemistry. Supplement

JF - Journal of Cellular Biochemistry. Supplement

SN - 0733-1959

IS - 12

ER -