Tissue inhibitor of metalloproteinase-2 (TIMP-2) has erythroid-potentiating activity.
Tissue inhibitor of metalloproteinase (TIMP) was purified and molecularly cloned on the basis of its erythroid-potentiating activity (EPA). TIMP/EPA appears to be a bifunctional molecule with both growth factor and anti-enzymatic activity. Recently, a second TIMP-related molecule was identified and we have investigated its possible erythroid-potentiating activity. Native, purified human TIMP-2 was assayed for erythroid-potentiating activity using an in vitro erythroid burst formation assay and was compared with that of previously characterized recombinant EPA/TIMP-1. The results demonstrate that both members of the tissue inhibitor of metalloproteinase family, TIMP-1 and TIMP-2, possessed erythroid potentiating activity which was inhibited by antibodies developed to neutralize EPA. These results suggest that TIMP-2 shares a common structural domain with EPA/TIMP-1 that is responsible for the erythroid-potentiating activity of these inhibitors. Therefore, TIMP-1 and TIMP-2, with both anti-protease activity and growth factor activity, join a family of bifunctional molecules such as fibroblast growth factor and thrombin which have both enzymatic and growth factor activity.
Stetler-Stevenson
W G
WG
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Bersch
N
N
Golde
D W
DW
D002352:Carrier Proteins / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D000939:Epitopes; D004920:Erythropoiesis / Q000187:drug effects*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D009363:Neoplasm Proteins / Q000276:immunology / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013329:Structure-Activity Relationship; D019716:Tissue Inhibitor of Metalloproteinase-2
D002352:Carrier Proteins; D000939:Epitopes; D006133:Growth Substances; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2