Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin

Leslie Pomeraniec, Melissa Hector-Greene, Marcelo Ehrlich, Gerard C. Blobe, Yoav I. Henis*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Complex formation among transforming growth factor-β (TGF-β) receptors and its modulation by coreceptors represent an important level of regulation for TGF-β signaling. Oligomerization of ALK5 and the type II TGF-β receptor (TβRII) has been thoroughly investigated, both in vitro and in intact cells. However, such studies, especially in live cells, are missing for the endothelial cell coreceptor endoglin and for the ALK1 type I receptor, which enables endothelial cells to respond to TGF-β by activation of both Smad2/3 and Smad1/5/8. Here we combined immunoglobulin G-mediated immobilization of one cell-surface receptor with lateral mobility studies of a coexpressed receptor by fluorescence recovery after photobleaching (FRAP) to demonstrate that endoglin forms stable homodimers that function as a scaffold for binding TβRII, ALK5, and ALK1. ALK1 and ALK5 bind to endoglin with differential dependence on TβRII, which plays a major role in recruiting ALK5 to the complex. Signaling data indicate a role for the quaternary receptor complex in regulating the balance between TGF-β signaling to Smad1/5/8 and to Smad2/3.

Original languageEnglish
Pages (from-to)3117-3127
Number of pages11
JournalMolecular Biology of the Cell
Issue number17
StatePublished - 1 Sep 2015


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