Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors
Department of Biochemistry
Binding, Competitive; Cell Line; Cell Membrane; Growth Substances; Humans; Kinetics; Macromolecular Substances; Peptides; Receptors, Cell Surface; Receptors, Transforming Growth Factor beta; Transforming Growth Factors
Life Sciences | Medicine and Health Sciences
Type beta transforming growth factors (TGF) are disulfide-linked homo- and heterodimers of two related polypeptide chains, beta 1 and beta 2. The homodimers TGF-beta 1 and TGF-beta 2 are widely distributed, but the heterodimer TGF-beta 1.2 has been found only in porcine platelets (Cheifetz, S., Weatherbee, J.A., Tsang, M.L.-S., Anderson, J.K., Mole, J.E., Lucas, R., and Massague, J. (1987) Cell 48, 409-415). Here we characterize the receptor binding and biological properties of TGF-beta 1.2 and compare them with those of TGF-beta 1 and TGF-beta 2. Three types of cell surface receptors previously identified by affinity labeling with 125I-TGF-beta 1 are available for binding to TGF-beta 1.2. These three types of receptors are detected as 65-kDa (type I), 85-95-kDa (type II), and 250-350-kDa (type III) affinity-labeled receptor complexes on electrophoresis gels. They co-exist in many cell types, have high affinity for TGF-beta 1, and varying degrees of affinity for TGF-beta 2. Of the 11 cell lines screened in the present study none showed evidence for additional receptor types that would bind TGF-beta 2 but not TGF-beta 1. In receptor competition studies, TGF-beta 1, TGF-beta 1.2, and TGF-beta 2 competed for binding to type I and type II receptors with a relative order of potencies of 16:5:1 and 12:3:1, respectively, whereas all three forms of TGF-beta were equipotent as ligands for the type III receptors. The three forms of TGF-beta were equally potent at stimulating the biosynthesis of extracellular sulfated proteoglycan in BRL-3A rat liver epithelial cells, a response that presumably involves the type III receptor present in these cells. In contrast, the ability of the three ligands to inhibit the growth of B6SUt-A multipotential hematopoietic progenitor cells which display only type I receptors decreased in the order TGF-beta 1, TGF-beta 1.2, and TGF-beta 2 with a relative potency of 100:30:1. The results indicate that the presence of one beta 1 chain in TGF-beta 1.2 increases (with respect to TGF-beta 2) the biological potency and binding affinity toward receptor types I and II, but the presence of a second beta 1 chain in the dimer is required for full potency.
J Biol Chem. 1988 Aug 5;263(22):10783-9.
The Journal of biological chemistry
Cheifetz S, Bassols A, Stanley K, Ohta M, Greenberger JS, Massague J. (1988). Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors. Open Access Articles. Retrieved from https://escholarship.umassmed.edu/oapubs/892