Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation Meltem Sariahmetoglu * ,‡ , Bryan D. Crawford * , Hernando Leon † , Jolanta Sawicka * , Laiji Li § , Barbara J. Ballermann § , Charles Holmes ‡ , Luc G. Berthiaume || , Andrew Holt * , Grzegorz Sawicki * ,1 and Richard Schulz * ,† ,2 Departments of Pharmacology, * Pediatrics, † Biochemistry, ‡ Medicine, § and Cell Biology, || Cardiovascular Research Group, University of Alberta, Edmonton, Alberta, Canada 2 Correspondence: Departments of Pediatrics and Pharmacology, 462 Heritage Medical Research Center, University of Alberta, Edmonton, AB T6G 2S2, Canada, E-mail: richard.schulz@ualberta.ca The regulation of matrix metalloproteinases (MMP) has been studied extensively due to the fundamental roles these zinc-endopeptidases play in diverse physiological and pathological processes. However, phosphorylation has not previously been considered as a potential modulator of MMP activity. The ubiquitously expressed MMP-2 contains 29 potential phosphorylation sites. Mass spectrometry reveals that at least five of these sites are phosphorylated in hrMMP-2 expressed in mammalian cells. Treatment of HT1080 cells with an activator of protein kinase C results in a change in MMP-2 immunoreactivity on 2D immunoblots consistent with phosphorylation, and purified MMP-2 is phosphorylated by protein kinase C in vitro . Furthermore, MMP-2 from HT1080 cell-conditioned medium is immunoreactive with antibodies directed against phosphothreonine and phosphoserine, which suggests that it is phosphorylated. Analysis of MMP-2 activity by zymography, gelatin dequenching assays, and measurement of kinetic parameters shows that the phosphorylation status of MMP-2 significantly affects its enzymatic properties. Consistent with this, dephosphorylation of MMP-2 immunoprecipitated from HT1080 conditioned medium with alkaline phosphatase significantly increases its activity. We conclude that MMP-2 is modulated by phosphorylation on multiple sites and that protein kinase C may be a regulator of this protease in vivo . Key Words: dephosphorylation • gelatinase • alkaline phosphate • protein kinase C • mass spectrometry
End of preview. The entire article is 10 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/regulation-of-matrix-metalloproteinase-2-mmp-2-activity-by-Wzir6F5O6q
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
Regulation of matrix metalloproteinase-2 (MMP-2) activity by phosphorylation
Sariahmetoglu, Meltem; Crawford, Bryan D.; Leon, Hernando; Sawicka, Jolanta; Li, Laiji; Ballermann, Barbara J.; Holmes, Charles; Berthiaume, Luc G.; Holt, Andrew; Sawicki, Grzegorz; Schulz, Richard
Follow The FASEB Journal
, Volume 21 (10): 2486
Fed of American Socs for Experimental Biology – Aug 1, 2007
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
