A single heteromeric receptor complex is sufficient to mediate biological effects of transforming growth factor-beta ligands.

Published

Journal Article

Transforming growth factor beta (TGF-beta), a multifunctional cytokine that regulates a variety of biological functions, signals through a heteromeric receptor complex of the type I and type II TGF-beta receptors. The type II receptor, a transmembrane serine-threonine kinase, was cloned based on its ability to directly bind TGF-beta. Recently, a number of candidate type I TGF-beta receptors have been isolated. Although only one of these transmembrane kinases (R4) has been shown to mediate TGF-beta-dependent gene activation, others bind TGF-beta when overexpressed in COS cells. Consequently, it has been postulated that the diversity of TGF-beta responses is generated through the association of distinct type I receptors with the type II TGF-beta receptor, thus creating receptor complexes of differential signaling capacities. In contrast to this model, we demonstrate that stable expression of only the R4 type I TGF-beta receptor in a mutant cell line lacking endogenous type I TGF-beta receptor was able to complex with the endogenous type II TGF-beta receptor and restore the effects of TGF-beta on inhibition of cell proliferation and activation of specific genes, regardless of which of the three mammalian isoforms of TGF-beta was used as the ligand. Therefore, R4 acts as a fully functional type I TGF-beta receptor, and the differential effects of TGF-beta are likely mediated by a single receptor complex consisting of R4 and the type II receptor.

Full Text

Duke Authors

Cited Authors

  • Bassing, CH; Howe, DJ; Segarini, PR; Donahoe, PK; Wang, XF

Published Date

  • May 27, 1994

Published In

Volume / Issue

  • 269 / 21

Start / End Page

  • 14861 - 14864

PubMed ID

  • 8195115

Pubmed Central ID

  • 8195115

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng

Conference Location

  • United States