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Characterization of plasma gelsolin as a substrate for matrix metalloproteinases
Author(s) -
Park SungMin,
Hwang In Kwan,
Kim Se Yeon,
Lee SeoJin,
Park KangSik,
Lee SeungTaek
Publication year - 2006
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200500402
Subject(s) - gelsolin , matrix metalloproteinase , extracellular matrix , cleavage (geology) , extracellular , actin , chemistry , proteolysis , biochemistry , metalloproteinase , peptide , biology , enzyme , paleontology , fracture (geology)
We previously showed that plasma gelsolin, a major component of the extracellular actin scavenging system, is an matrix metalloproteinase (MMP)‐14 substrate. Here we confirmed that plasma gelsolin is cleaved by MMP‐14 at the plasma level, and found that it was most efficiently digested by MMP‐3 followed by MMP‐2, MMP‐1, MMP‐14, and MMP‐9, in that order. Plasma gelsolin (90 kDa) was cut into several fragments of 43–48 kDa by MMP‐3. The MMP‐3 cleavage sites in plasma gelsolin were determined by labeling the C termini generated by in‐gel digestion with 50% H 2 18 O combined with peptide mass mapping, and sequencing of the N‐terminal amino acids. Plasma gelsolin was cleaved at Asn 416 ‐Val 417 , Ser 51 ‐Met 52 , and Ala 435 ‐Gln 436 .Proteolytic cleavage by MMP‐3 resulted in considerable loss of its actin filament‐depolymerizing activity. This suggests that MMPs weaken the extracellular actin‐scavenging system by cleaving plasma gelsolin and may, therefore, be involved in pathological conditions induced by extracellular actin, such as endothelial injury, respiratory distress syndrome, hepatic necrosis, and septic shock.