TβRIII independently binds type I and type II TGF-β receptors to inhibit TGF-β signaling.


Journal Article

Transforming growth factor-β (TGF-β) receptor oligomerization has important roles in signaling. Complex formation among type I and type II (TβRI and TβRII) TGF-β receptors is well characterized and is essential for signal transduction. However, studies on their interactions with the type III TGF-β coreceptor (TβRIII) in live cells and their effects on TGF-β signaling are lacking. Here we investigated the homomeric and heteromeric interactions of TβRIII with TβRI and TβRII in live cells by combining IgG-mediated patching/immobilization of a given TGF-β receptor with fluorescence recovery after photobleaching studies on the lateral diffusion of a coexpressed receptor. Our studies demonstrate that TβRIII homo-oligomerization is indirect and depends on its cytoplasmic domain interactions with scaffold proteins (mainly GIPC). We show that TβRII and TβRI bind independently to TβRIII, whereas TβRIII augments TβRI/TβRII association, suggesting that TβRI and TβRII bind to TβRIII simultaneously but not as a complex. TβRIII expression inhibited TGF-β-mediated Smad2/3 signaling in MDA-MB-231 cell lines, an effect that depended on the TβRIII cytoplasmic domain and did not require TβRIII ectodomain shedding. We propose that independent binding of TβRI and TβRII to TβRIII competes with TβRI/TβRII signaling complex formation, thus inhibiting TGF-β-mediated Smad signaling.

Full Text

Duke Authors

Cited Authors

  • Tazat, K; Hector-Greene, M; Blobe, GC; Henis, YI

Published Date

  • October 1, 2015

Published In

Volume / Issue

  • 26 / 19

Start / End Page

  • 3535 - 3545

PubMed ID

  • 26269580

Pubmed Central ID

  • 26269580

Electronic International Standard Serial Number (EISSN)

  • 1939-4586

Digital Object Identifier (DOI)

  • 10.1091/mbc.E15-04-0203


  • eng

Conference Location

  • United States