Cells regulate their mitogenic response to thrombin through release of protease nexin.
We previously reported that human and mouse fibroblast-like cells release into their growth medium a protein that we termed protease nexin. Protease nexin forms a covalent acyl linkage with thrombin and certain other serine proteases via the protease active site and mediates their binding, internalization and degradation by cells. Binding of thrombin-protease nexin to cells is mediated by the protease nexin portion of the complex to a high-affinity cellular binding site. As thrombin is a potent mitogen for a variety of fibroblast-like cells in culture, we examined whether protease nexin itself regulates thrombin-stimulated cell division. Recently, we showed that heparin virtually blocked the binding of thrombin-protease nexin complexes to both mouse and human cells without affecting the ability of these cells to respond to thrombin. Thus, protease nexin does not appear to be a positive modulator in thrombin-induced cell division. Here, we show that protease nexin negatively regulates the mitogenic response of cells in culture to thrombin.
D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002352:Carrier Proteins / Q000494:pharmacology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002478:Cells, Cultured; D006224:Cricetinae; D003470:Culture Media; D005347:Fibroblasts / Q000187:drug effects; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008934:Mitogens; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology*
D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D003470:Culture Media; D008934:Mitogens; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D006493:Heparin; D013917:Thrombin