The transforming growth factor β receptors types I, II, and III form hetero-oligomeric complexes in the presence of ligand

Aristidis Moustakas, Herbert Y. Lin, Yoav I. Henis, Josée Plamondon, Maureen D. O'Connor-McCourt, Harvey F. Lodish*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Transforming growth factors β (TGF-βs) are disulfide-linked dimers. In Rat-1 cells both radioiodinated TGF-β1 and -β2 bind to and can be chemically cross-linked to type I and II receptors (which are thought to mediate effects of cell growth suppression and gene activation), to type III proteoglycan receptors, and to a novel ∼50-kDa protein. After detergent solubilization of cells that were cross-linked with radioiodinated TGF-∼, antibodies specific for the type II receptor precipitated labeled receptor types I and III as well as type II. In these cells, the type III receptor is the predominant TGF-β-binding protein, and antibodies specific for it precipitate mainly this cross-linked receptor. Thus, in the presence of TGF-β ligand, receptor types II and III and types II and I form heteromeric complexes. The majority of the type III receptor does not associate with receptor types I and II, probably reflecting the relative amounts of the three receptors on the surface of Rat-1 cells. Since TGF-β1 but not TGF-β2 binds to the exoplasmic domain of the type II receptor in the absence of the type III receptor, and since both TGF-β1 and -β2 bind with high affinity to the type III receptor, we suggest that TGF-β2, and possibly TGF-β1, bind initially to the type III receptor. The TGF-β2-type III receptor complex would then interact with a type II receptor, thus modulating the affinity of the type II receptor for TGF-β2.

Original languageEnglish
Pages (from-to)22215-22218
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number30
StatePublished - 25 Oct 1993

Funding

FundersFunder number
National Heart, Lung, and Blood InstituteP01HL041484

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