Tissue Inhibitor of Metalloproteinase
In mammals, the tissue inhibitor of metalloproteinase (TIMP) family is comprised of four members, TIMP1-4. TIMPs are the primary inhibitors of metalloproteinases, such as the matrix metalloprotease (MMP) family, a disintegrin and metalloproteinase (ADAM) family, and the ADAMs with thrombospondin motifs (ADAMTS) family (Brew and Nagase 2010). TIMPs range in size from 22 to 28 kDA and are variably glycosylated (Murphy 2011). Further, each TIMP contains two distinct domains, an N-terminal and C-terminal domain of ~125 and 65 amino acids, respectively, connected through six conserved disulfide bonds (Brew and Nagase 2010; Murphy 2011). Each of these domains has critical roles in controlling TIMP function and localization.
The N-terminal domain, which folds independently and is composed of three α helices and five β strands arranged in a twisted β barrel, is critical for the inhibition of...
KeywordsVascular Endothelial Growth Factor Focal Adhesion Kinase Endothelial Cell Proliferation TIMP3 Expression Increase MMP14 Activity
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