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.
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.
Segarini
P R
PR
Department of Cellular and Molecular Biology, Celtrix Laboratories, Palo Alto, California 94303.
Ziman
J M
JM
Kane
C J
CJ
Dasch
J R
JR
D000345:Affinity Labels; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D002645:Chickens; D006224:Cricetinae; D003432:Cross-Linking Reagents; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D006868:Hydrolysis; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D000345:Affinity Labels; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D016212:Transforming Growth Factor beta