Sequence of human tissue inhibitor of metalloproteinases and its identity to erythroid-potentiating activity.
Collagen fibres form the stable architecture of connective tissues and their breakdown is a key irreversible step in many pathological conditions. The destruction of collagen is usually initiated by proteinases, the best known of which is the metalloproteinase collagenase (EC 3.4.24). Collagenase and related metalloproteinases are regulated at the level of their synthesis and secretion, through the action of specific stimuli such as hormones and cytokines, and also at the level of their extracellular activity through the action of a specific inhibitor, TIMP (tissue inhibitor of metalloproteinases), which irreversibly forms inactive complexes with metalloproteinases. Although the mechanisms governing the production of TIMP are unknown, immunologically identical forms of this glycoprotein have been detected in a wide variety of human body fluids and cell and tissue culture media. We therefore suggested that under physiological conditions this ubiquitous inhibitor predominates over active metalloproteinases and that tissue destruction may arise when any perturbation of this controlling excess arises. However, further progress towards testing this theory has been hindered by a lack of knowledge about the structure of TIMP and insufficient material for studying it in model systems. Here we describe the structure of TIMP predicted from its complementary DNA, its synthesis in Escherichia coli and transfected animal cells, and the finding that it is identical to a protein recently reported to have erythroid-potentiating activity (EPA).
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004791:Enzyme Inhibitors; D004920:Erythropoiesis; D004926:Escherichia coli / Q000235:genetics; D006801:Humans; D011061:Poly A / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases
D004791:Enzyme Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D011061:Poly A; D004247:DNA