Disease relevance of MGP

• Here we have demonstrated the adherence of chondrocytes, fibroblasts, osteosarcoma cells, and kidney mesangial cells to MGP purified from bovine bone [1].
• Matrix GLA protein (MGP) deficient mice develop severe vascular calcification and die prematurely from heart failure and/or aortic rupture [2].

High impact information on MGP

• The results suggest that the effects of BMP on endothelial cells occur in part through induction of ALK1, an effect that may be limited by ALK1-induced MGP [3].
• Neutralizing antibodies to TGF-beta blocked the effect of MGP on VEGF expression [4].
• The additional evidence previously adduced in support of the putative cell adhesion activity of MGP is that heat decarboxylation of the vitamin K-dependent gamma-carboxyglutamate residues in MGP abolished the adhesion activity [5].
• Matrix Gla protein (MGP) is a 14-kDa protein found in bone and cartilage which contains the unusual amino acid gamma-carboxyglutamic acid (Gla) [1].
• However, the Arg-Gly-Asp-containing synthetic peptide Gly-Arg-Gly-Asp-Ser-Pro significantly inhibited cell attachment to MGP, whereas the control peptide Gly-Arg-Gly-Glu-Ser-Pro had minimal effect [1].

Biological context of MGP

• The complete amino acid sequence of bovine bone matrix Gla protein (MGP) was determined by automatic sequence analysis of the intact protein and of peptides isolated from tryptic and BNPS-skatole digests [6].
• Recent studies have shown that MGP is strongly induced by retinoic acid in fibroblasts, chondrocytes, and osteoblasts, a response which suggests that MGP mediates an action of retinoic acid on an aspect of cell growth or differentiation [7].
• This shortened version of human MGP is consistent with the proposed model for COOH-terminal processing, since the amino acid substitution in the COOH terminus of the human protein, Lys79 for Gln79, would allow removal of the additional basic residues from the human MGP COOH terminus by the action of the carboxypeptidase B-like enzymic activity [7].
• There is sufficient sequence homology between MGP and bone Gla protein (BGP) to indicate that these two bovine bone proteins arose by gene duplication and subsequent divergent evolution [6].
• The recognition motif found for MGP phosphorylation, Ser-X-Glu/Ser(P), has been seen previously in milk caseins, salivary proteins, and a number of regulatory peptides [8].

Anatomical context of MGP

• Matrix GLA protein (MGP) is expressed in endothelial cells (EC), and MGP deficiency results in developmental defects suggesting involvement in EC function [4].
• Since essentially equal amounts of the 79- and 83-residue forms of MGP were also detected in bovine articular cartilage and plasma, it seems likely that the COOH-terminal processing events identified in bone apply to many of the other tissues which synthesize this protein [7].
• Mg2+ and Mn2+ supported attachment to all three ECM proteins but Ca2+ did not support attachment to collagen and was less effective than Mg2+ or Mn2+ in chondrocyte attachment to MGP [9].
• In long bone diaphyses, total levels of MGP were essentially equivalent in newborn, juvenile, and adult rats [10].
• Northern analysis and immunohistochemistry demonstrated that MGP was only expressed by pericytes in calcified nodules [11].

Associations of MGP with chemical compounds

• The presence of NH2-terminal Glu residues between the putative targeting domain for the gamma-carboxylase in the MGP leader sequence and the mid-molecule Gla residues suggests that the gamma-carboxylase may have additional, as yet unrecognized, specificity requirements which determine the susceptibility of Glu residues for gamma-carboxylation [6].
• Two forms of MGP were isolated from demineralization and urea extracts of bovine cortical bone, one 79 residues in length with the COOH terminus Phe-Arg-Gln and the other 83 residues in length with the COOH terminus Phe-Arg-Gln-Arg-Arg-Gly-Ala [7].
• In this study, attachment assays were used to examine integrin-mediated attachment of chondrocytes to fibronectin, matrix Gla protein (MGP), and type II collagen [9].
• Phosphoserine was identified at residues 3, 6, and 9 of bovine, human, rat, and lamb MGP by N-terminal protein sequencing [8].
• Two of the serines phosphorylated in shark MGP, residues 2 and 5, also have glutamate residues in the n + 2 position in tandemly repeated Ser-X-Glu sequences, whereas the third, shark residue 3, would acquire an acidic phosphoserine in the n + 2 position upon phosphorylation of serine 5 [8].

Other interactions of MGP

• Together, the results suggest that MGP plays a role in EC function, altering the response to TGF-beta superfamily growth factors [4].
• A plausible sequence of proteolytic cleavages that could generate the 79-residue form of MGP would be a trypsin-like cleavage at Arg80-Arg81 or Arg81-Gly82 followed by carboxypeptidase B-like cleavage to remove COOH-terminal arginine(s) [7].
• Seven days of retinoic acid treatment resulted in decreased attachment to fibronectin, MGP, and collagen [9].
• Matrix Gla protein, a new gamma-carboxyglutamic acid-containing protein which is associated with the organic matrix of bone [12].

Analytical, diagnostic and therapeutic context of MGP

• To further characterize the MGP antigen in bone, extracts from newborn and adult rat bones were chromatographed by gel filtration over Sephacryl S-200 [10].
• The radioimmunoassay for rat MGP which was developed for these studies employs rabbit antibody directed against calf MGP and rat MGP for standards and radioiodinated tracer [10].
• Matrix GLA protein (MGP), also expressed in atherosclerotic lesions, was added to CVC in coculture [13].

References