RRC ID 64204
Author Hayakawa T, Yamashita K, Ohuchi E, Shinagawa A.
Title Cell growth-promoting activity of tissue inhibitor of metalloproteinases-2 (TIMP-2).
Journal J Cell Sci
Abstract Human tissue inhibitor of metalloproteinases-2 (TIMP-2) has a potent growth-promoting activity for wide range of human, bovine and mouse cells, having an optimal concentration (10 ng/ml, 0.46 nM) that is ten-times lower than that of TIMP-1 (Hayakawa et al. (1992) FEBS Lett. 298, 29). Neither TIMP-1 complexed with progelatinase B nor TIMP-2 complexed with progelatinase A, both of which have full inhibitory activity against active forms of matrix metalloproteinases (MMPs), showed any cell growth-promoting activity. On the contrary, both reductively alkylated TIMPs had no MMP inhibitory activity, but significantly stimulated cell proliferation. These facts clearly indicate that the cell-proliferation. These facts clearly indicate that the cell-proliferating activity of TIMPs is independent of MMP inhibitory activity. We also demonstrated that [3H]thymidine was significantly incorporated into Raji cells, a Burkitt lymphoma cell line, in the presence of either 4 ng/ml of TIMP-1 or 0.1 ng/ml of TIMP-2. Under steady-state conditions at 4 degrees C, high-(Kd = 0.15 nM) and low-(35 nM) affinity binding sites for TIMP-2 were identified on Raji cells with 20,000 and 1.4 x 10(5) sites/cell, respectively. Both high- and low-affinity binding of 125I-TIMP-2 to Raji cells were competitively inhibited by unlabeled TIMP-2 but not by unlabeled TIMP-1, suggesting the presence of receptors for TIMP-2 independent from those for TIMP-1. TIMP-2 seems to be another new TIMP cell-growth factor in serum, besides TIMP-1.
Volume 107 ( Pt 9)
Pages 2373-9
Published 1994-9-1
DOI 10.1242/jcs.107.9.2373
PMID 7844157
MeSH Alkylation Animals CHO Cells Cattle Cell Division / drug effects Cell Membrane / drug effects Cells, Cultured / drug effects Cricetinae DNA Replication / drug effects Enzyme Precursors / metabolism Extracellular Matrix Proteins / antagonists & inhibitors Fibroblasts / drug effects Fibroblasts / metabolism Gelatinases / metabolism Glycoproteins / pharmacology Humans Metalloendopeptidases / antagonists & inhibitors Metalloendopeptidases / metabolism Mice Oxidation-Reduction Proteins / pharmacology* Stimulation, Chemical Tissue Inhibitor of Metalloproteinase-2 Tissue Inhibitor of Metalloproteinases Tumor Cells, Cultured / drug effects
IF 4.573
Human and Animal Cells CHO-K1(RCB0285) J774.1(RCB0434) K562(RCB0027)