Two novel patterns of transforming growth factor beta (TGF-beta) binding to cell surface proteins are dependent upon the binding of TGF-beta 1 and indicate a mechanism of positive cooperativity

• Published in: The Journal of biological chemistry 1992-01, Vol.267 (2), p.1048-1053
• Main Authors: Segarini, P R, Ziman, J M, Kane, C J, Dasch, J R
• Format: Article
• Language: English
• Subjects: Affinity Labels; Animals; Autoradiography; Binding, Competitive; Cattle; Cells, Cultured; Chickens; Cricetinae; Cross-Linking Reagents; Electrophoresis, Polyacrylamide Gel; Glycosylation; Humans; Hydrolysis; Kidney - cytology; Kidney - metabolism; Membrane Proteins - metabolism; Muscle, Smooth - cytology; Muscle, Smooth - metabolism; Muscles - cytology; Muscles - metabolism; Rats; Transforming Growth Factor beta - metabolism; transforming growth factor- beta; transforming growth factor- beta 1
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)48393-7

Three isoforms of the transforming growth factor beta (TGF-beta) family, TGF-beta 1, TGF-beta 2, and TGF-beta 3, bind specifically and with high affinity to several cell surface components known as type I, type II, and type III proteins. The type I and II proteins may serve as biological receptors, whereas the type III protein does not appear to be associated with TGF-beta-mediated cell responses, and its function remains unknown. Binding data on confluent monolayers of rat skeletal myoblasts of the L6 cell line reveals two novel patterns of TGF-beta 1 binding. Saturation of the type I receptor with native TGF-beta 2 induces a 7-fold increase in binding of radiolabeled TGF-beta 1 at the type II protein. No induction of type II receptor binding was observed on subconfluent cells indicating a density-dependent phenomenon. The data suggest that the type I and type II proteins may interact during ligand binding in a manner which may be indicative of a regulatory role that is activated by the phase of cell growth or differentiation. A second observation is the binding of TGF-beta to a glycoprotein of 180 kDa and referred to here as the “type VI” binding protein. This protein is not related to previously described TGF-beta binding proteins, and its distribution appears universal among cell types. The level of TGF-beta 1 binding to this protein is dependent on the presence of TGF-beta 2. It is not known whether this protein transmits biological information or whether it serves as an accessory protein of a TGF-beta receptor complex.