FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin |
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Authors: | Gitte N Schytte Brian Christensen Ida Bregenov Katarzyna Kjøge Carsten Scavenius Steen V Petersen Jan J Enghild Esben S Sørensen |
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Institution: | 1. Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark;2. Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark
Interdisciplinary Nanoscience Center, Aarhus University, Aarhus, Denmark;3. Department of Biomedicine, Aarhus University, Aarhus, Denmark |
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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 143RGDSVVYGLR152 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 αvβ3 integrin in MDA-MB-435 and Moαv cells. This suggests a new mechanism by which specific phosphorylation of OPN can regulate interaction with the αvβ3 integrin and thereby affect OPN-cell interaction. |
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Keywords: | FAM20C osteopontin phosphorylation αvβ3 integrin |
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