Transforming growth factor-beta receptors and binding proteoglycans.
Transforming growth factors-beta (TGFs-beta) are representative of a superfamily whose members were first identified as regulators of morphogenesis and differentiation, and subsequently found to be structurally related. Other members of the family include the activins and inhibins, BMPs, MIS, the DPP-C gene product and Vg-1. When assayed by affinity-labelling techniques, TGFs-beta bind to three distinct cell surface proteins which are present on most cells. These proteins are all of relatively low abundance but bind TGFs-beta with affinities consistent with the biological potency of the factors. The Type I and Type II binding proteins are glycoproteins with estimated molecular weights of 53 and 73 x 10(3) Mr, respectively. They both bind TGF-beta 1 significantly better than TGF-beta 2. The Type I receptor has been identified as the receptor which mediates many of the responses of TGFs-beta, based on somatic cell genetic studies of epithelial cell mutants unresponsive to TGFs-beta. Betaglycan is the third binding protein present on many, but not all, cell types and is a large proteoglycan (approximately 280 x 10(3) Mr) with 100-120 x 10(3) Mr core proteins. A soluble form of this molecule is present in conditioned media of many cell lines and may be derived from the cell surface-associated molecule by cleavage of a small membrane anchor. Betaglycan binds TGF-beta 1 and TGF-beta 2 with similar affinity and this binding is to the core proteins, not the glycosaminoglycan side chains. This molecule may have a function in the localization and delivery or the clearance of activated TGFs-beta.(ABSTRACT TRUNCATED AT 250 WORDS)
Boyd
F T
FT
Cell Biology and Genetics Program, Memorial Sloan-Kettering Cancer Center, Sloan-Kettering Division of the Graduate School of Medical Sciences, Cornell University, New York, New York 10021.
Cheifetz
S
S
Andres
J
J
Laiho
M
M
Massagué
J
J
D000818:Animals; D002460:Cell Line; D006801:Humans; D011509:Proteoglycans / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000502:physiology*
D011509:Proteoglycans; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta