Transforming growth factor-β receptors and binding proteoglycans

F. T. Boyd, S. Cheifetz, J. Andres, M. Laiho, J. Massague

Research output: Contribution to journalArticle

Abstract

Transforming growth factors-beta (TGFs-β) 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-β bind to three distinct cell surface proteins which are present on most cells. These proteins are all of relatively low abundance but bind TGFs-β 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 103 M(r), respectively. They both bind TGF-β1 significantly better than TGF-β2. The Type I receptor has been identified as the receptor which mediates many of the responses of TGFs-β, based on somatic cell genetic studies of epithelial cell mutants unresponsive to TGFs-β. Betaglycan is the third binding protein present on many, but not all, cell types and is a large proteoglycan (~280 x 103 M(r)) with 100-120 x 103 M(r) 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-β1 and TGF-β2 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-β. The molecular basis of TGF-β signalling is still largely unknown, but it is possible that one or more of these cell surface molecules signals via a novel mechanism, as the TGFs-β are biologically quite distinct from other factors that act via well-characterized signalling systems.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalJournal of cell science
Volume97
Issue numberSUPPL. 13
DOIs
StatePublished - 1990

Keywords

  • Receptors Binding proteoglycans
  • Transforming growth factor-beta (TGF-β)

ASJC Scopus subject areas

  • Cell Biology

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