Document Detail

Regulation of ATPase activity of transglutaminase 2 by MT1-MMP: implications for mineralization of MC3T3-E1 osteoblast cultures.
MedLine Citation:
PMID:  20049897     Owner:  NLM     Status:  MEDLINE    
A pro-mineralization function for transglutaminase 2 (TG2) has been suggested in numerous studies related to bone, cartilage, and vascular calcification. TG2 is an enzyme which can perform protein crosslinking functions, or act as a GTPase/ATPase depending upon different stimuli. We have previously demonstrated that TG2 can act as an ATPase in a Ca(2+)-rich environment and that it can regulate phosphate levels in osteoblast cultures. In this study, we investigate the role MT1-MMP in regulating the ATPase activity of TG2. We report that proteolytic cleavage of TG2 by MT1-MMP in vitro results in nearly a 3-fold increase in the ATPase activity of TG2 with a concomitant reduction in its protein-crosslinking activity. We show that MC3T3-E1 osteoblasts secreted full-length TG2 and major smaller fragments of 66 and 56 kDa, the latter having ATP-binding abilities. MT1-MMP inhibition by a neutralizing antibody suppressed mineralization of osteoblast cultures to 35% of control, and significantly reduced phosphate levels in conditioned medium (CM). Furthermore, MT1-MMP inhibition abolished two of TG2 fragments in the cultures, one of which, the 56-kDa fragment, has ATPase activity. Neutralization of MT1-MMP at early phases of mineralization significantly reduced mineral deposition, but had no effect in later phases implying MT1-MMP and TG2 might contribute to the initiation of mineralization. The cleavage of TG2 by MT1-MMP likely occurs on the cell surface/pericellular matrix where MT1-MMP and TG2 were co-localized. Based on these data, we propose that MT1-MMP modulates the extracellular function TG2 as part of a regulatory mechanism activates the pro-mineralization function of TG2.
Yukiko Nakano; Jennifer Forsprecher; Mari T Kaartinen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular physiology     Volume:  223     ISSN:  1097-4652     ISO Abbreviation:  J. Cell. Physiol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-03-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0050222     Medline TA:  J Cell Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  260-9     Citation Subset:  IM    
Copyright Information:
J. Cell. Physiol. 223: 260-269, 2010. (c) 2009 Wiley-Liss, Inc.
Division of Biomedical Sciences, Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
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MeSH Terms
3T3 Cells
Adenosine Triphosphate / metabolism
Binding Sites
Calcification, Physiologic*
Calcium / metabolism
Enzyme Activation
GTP-Binding Proteins / chemistry,  metabolism*
Matrix Metalloproteinase 14 / metabolism*
Molecular Weight
Osteoblasts / enzymology*
Peptide Fragments
Phosphates / metabolism
Protein Processing, Post-Translational
Time Factors
Transglutaminases / chemistry,  metabolism*
Grant Support
MOP-85024//Canadian Institutes of Health Research; MOP-89827//Canadian Institutes of Health Research
Reg. No./Substance:
0/Mmp14 protein, mouse; 0/Peptide Fragments; 0/Phosphates; 56-65-5/Adenosine Triphosphate; 7440-70-2/Calcium; EC 2.3.2.-/transglutaminase 2; EC; EC Metalloproteinase 14; EC 3.6.1.-/GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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