Matches in SemOpenAlex for { <https://semopenalex.org/work/W2472319038> ?p ?o ?g. }
- W2472319038 abstract "The in vivo roles of meprin metalloproteases in pathophysiological conditions remain elusive. Substrates define protease roles. Therefore, to identify natural substrates for human meprin a and b we employed TAILS (terminal amine isotopic labeling of substrates), a proteomics approach that enriches for N-terminal peptides of proteins and cleav- age fragments. Of the 151 new extracellular substrates we identified, it was notable that ADAM10 (a disintegrin and metalloprotease domain-containing protein 10)—the consti- tutive a-secretase—is activated by meprin b through cleavage of the propeptide. To validate this cleavage event, we expressed recombinant proADAM10 and after preincu- bation with meprin b, this resulted in significantly elevated ADAM10 activity. Cellular expression in murine primary fibroblasts confirmed activation. Other novel substrates including extracellular matrix proteins, growth factors and inhibitors were validated by western analyses and enzyme activity assays with Edman sequencing confirming the exact cleavage sites identified by TAILS. Cleavages in vivo were confirmed by comparing wild-type and meprin -/- mice. Our finding of cystatin C, elafin and fetuin-A as substrates and natural inhibitors for meprins reveal new mechanisms in the regulation of protease activity important for understanding pathophysiological processes." @default.
- W2472319038 created "2016-07-22" @default.
- W2472319038 creator A5014052805 @default.
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- W2472319038 date "2012-01-01" @default.
- W2472319038 modified "2023-09-27" @default.
- W2472319038 title "The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin b and ADAM10 Tamara JeffersonUlrich auf dem KellerCaroline BellacVerena V. MetzClaudia Broder • Jana HedrichAnke OhlerWladislaw MaierViktor MagdolenErwin Sterchi • Judith S. BondArumugam JayakumarHeiko TraupeAthena ChalarisStefan Rose-John • Claus U. PietrzikRolf PostinaChristopher M. OverallChristoph Becker-Pauly" @default.
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- W2472319038 hasPublicationYear "2012" @default.
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