Tissue inhibitor of metalloproteinase-2 (TIMP-2) has erythroid-potentiating activity

FEBS Lett. 1992 Jan 20;296(2):231-4. doi: 10.1016/0014-5793(92)80386-u.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carrier Proteins / pharmacology
  • Cell Division / drug effects*
  • Epitopes
  • Erythropoiesis / drug effects*
  • Growth Substances / pharmacology*
  • Humans
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / pharmacology*
  • Recombinant Proteins / pharmacology
  • Structure-Activity Relationship
  • Tissue Inhibitor of Metalloproteinase-2


  • Carrier Proteins
  • Epitopes
  • Growth Substances
  • Neoplasm Proteins
  • Recombinant Proteins
  • Tissue Inhibitor of Metalloproteinase-2