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

Gitte N Schytte; Brian Christensen; Ida Bregenov; Katarzyna Kjøge; Carsten Scavenius; Steen V Petersen; Jan J Enghild; Esben S Sørensen

doi:10.1002/jcb.29708

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

Gitte N Schytte, Brian Christensen, Ida Bregenov, Katarzyna Kjøge, Carsten Scavenius, Steen V Petersen, Jan J Enghild, Esben S Sørensen^*

^*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

14 Citations (Scopus)

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.

Original language	English
Journal	Journal of Cellular Biochemistry
Volume	121
Issue	12
Pages (from-to)	4809-4818
Number of pages	10
ISSN	0730-2312
DOIs	https://doi.org/10.1002/jcb.29708
Publication status	Published - Dec 2020

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

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10.1002/jcb.29708

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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",

issn = "0730-2312",

publisher = "Wiley-Liss Inc.",

number = "12",

}

FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin. / Schytte, Gitte N; Christensen, Brian; Bregenov, Ida et al.
In: Journal of Cellular Biochemistry, Vol. 121, No. 12, 12.2020, p. 4809-4818.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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

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

SN - 0730-2312

VL - 121

SP - 4809

EP - 4818

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

IS - 12

ER -

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

Abstract

Keywords

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