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.
Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
W G
WG
Stetler-Stevenson
N
N
Bersch
D W
DW
Golde
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