Matrix Gla protein C-terminal region binds to vitronectin. Co-localization suggests binding occurs during tissue development.
Matrix Gla protein (MGP) regulates calcification in cartilage and arteries. MGP synthesis during embryonic development and its binding and regulation of growth factors and morphogens of the TGF-beta/BMP superfamily suggests that it has additional functions. Assay by far-western gel overlays and gel filtration shift shows MGP binds vitronectin. Binding is saturable and consistent with a single class of binding sites. MGP binds to vitronectin but not collagen, fibromodulin, heparin, osteocalcin, chondroitin sulfate, laminin, ovalbumin or albumin. We have identified a vitronectin binding site within a 17-amino acid peptide 61-77 near the carboxyl-terminus that corresponds to a naturally occurring MGP C-terminus. MGP and the 61-77 MGP peptide also binds to fibronectin. MGP and vitronectin are focally co-localized in embryonic tissues. Co-localization in vivo suggests that the MGP and vitronectin interactions may modify cell-matrix interactions. Alternatively, vitronectin-bound MGP may have altered function for modulating BMP2 or TGF-beta activity. The current study demonstrates that MGP has a novel binding activity for vitronectin, an extracellular protein that promotes cell-matrix interactions and regulates coagulation.
Department of Molecular Sciences, University of Tennessee Health Sciences Center, 858 Madison Avenue, Memphis, TN 38163, USA. snishimoto@utmem.edu
Satoru K
SK
Nishimoto
Miyako
M
Nishimoto
D000818:Animals; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D002356:Cartilage; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D047108:Embryonic Development; D016326:Extracellular Matrix Proteins / Q000737:chemistry* / Q000378:metabolism*; D005353:Fibronectins; D006801:Humans; D007668:Kidney; D011485:Protein Binding; D051381:Rats; D015203:Reproducibility of Results; D019096:Vitronectin / Q000378:metabolism*; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D019096:Vitronectin; D000097568:Matrix Gla Protein