title: Plasmin cleaves betaglycan and releases a 60 kDa transforming growth factor-beta complex from the cell surface.
abstract: Plasmin regulates the activity and distribution of transforming growth factor beta (TGF-beta) and other growth factors. The purpose of the present investigation was to determine the effects of plasmin on cellular receptors for TGF-beta. AKR-2B fibroblasts were affinity-labelled with 125I-TGF-beta 1 and 125I-TGF-beta 2, demonstrating betaglycan, the type-I TGF-beta receptor and the type-II TGF-beta receptor. Treatment of TGF-beta-affinity-labelled cells with plasmin (10-100 nM) for 1 h profoundly and selectively decreased recovery of TGF-beta-betaglycan complex. The type-I and type-II receptors were not plasmin substrates. A radiolabelled complex with an apparent mass of 60 kDa was detected by SDS/PAGE in both the medium and cell extracts of plasmin-treated affinity-labelled cells. In order to demonstrate that plasmin cleavage of betaglycan did not require prior exposure of the betaglycan to cross-linking agent, AKR-2B cells were treated with plasmin first and then affinity-labelled. Markedly decreased TGF-beta binding to cellular betaglycan was observed. Although plasmin treatment of AKR-2B cells decreased overall binding of 125I-TGF-beta 1 and 125I-TGF-beta 2, the rate at which the cells degraded bound 125I-TGF-beta at 37 degrees C was not changed. AKR-2B cells treated with plasmin demonstrated slightly increased [3H]thymidine incorporation; the plasmin-treated cells retained their ability to respond to TGF-beta. Conditioned medium from plasmin-treated AKR-2B cells contained increased amounts of active TGF-beta as determined in Mv 1 Lu epithelial-cell-proliferation assays. Specific cleavage of betaglycan represents a novel mechanism whereby plasmin may regulate the assortment of receptors available for TGF-beta. In addition, plasmin may facilitate transfer of active TGF-beta between neighbouring cells by releasing the active growth factor from the cell surface.
authors.affiliation: Department of Biomedical Sciences, University of Guelph, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Lamarre
authors.forename: J
authors.initials: J
authors.lastname: Vasudevan
authors.forename: S L
authors.initials: SL
authors.lastname: Gonias
mesh_terms: D000345:Affinity Labels; D001665:Binding Sites; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D017077:Culture Media, Conditioned; D005341:Fibrinolysin / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006868:Hydrolysis; D011509:Proteoglycans / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology
chemical_list: D000345:Affinity Labels; D017077:Culture Media, Conditioned; D006025:Glycosaminoglycans; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; C071736:betaglycan; D005341:Fibrinolysin