J. Biol. Chem., Vol. 263, Issue 22, 10783-10789, 08, 1988
Heterodimeric transforming growth factor beta. Biological properties and interaction with three types of cell surface receptors
S Cheifetz, A Bassols, K Stanley, M Ohta, J Greenberger and J Massague
Department of Biochemistry, University of Massachusetts Medical School, Worcester 01655.
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.
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