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

Publication ,  Journal Article
Pomeraniec, L; Hector-Greene, M; Ehrlich, M; Blobe, GC; Henis, YI
Published in: Mol Biol Cell
September 1, 2015

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.

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Published In

Mol Biol Cell

DOI

EISSN

1939-4586

Publication Date

September 1, 2015

Volume

26

Issue

17

Start / End Page

3117 / 3127

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Smad Proteins
  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Receptors, Cell Surface
  • Receptor, Transforming Growth Factor-beta Type I
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Humans
  • Fluorescence Recovery After Photobleaching
 

Citation

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Pomeraniec, L., Hector-Greene, M., Ehrlich, M., Blobe, G. C., & Henis, Y. I. (2015). Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin. Mol Biol Cell, 26(17), 3117–3127. https://doi.org/10.1091/mbc.E15-02-0069
Pomeraniec, Leslie, Melissa Hector-Greene, Marcelo Ehrlich, Gerard C. Blobe, and Yoav I. Henis. “Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin.Mol Biol Cell 26, no. 17 (September 1, 2015): 3117–27. https://doi.org/10.1091/mbc.E15-02-0069.
Pomeraniec L, Hector-Greene M, Ehrlich M, Blobe GC, Henis YI. Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin. Mol Biol Cell. 2015 Sep 1;26(17):3117–27.
Pomeraniec, Leslie, et al. “Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin.Mol Biol Cell, vol. 26, no. 17, Sept. 2015, pp. 3117–27. Pubmed, doi:10.1091/mbc.E15-02-0069.
Pomeraniec L, Hector-Greene M, Ehrlich M, Blobe GC, Henis YI. Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin. Mol Biol Cell. 2015 Sep 1;26(17):3117–3127.

Published In

Mol Biol Cell

DOI

EISSN

1939-4586

Publication Date

September 1, 2015

Volume

26

Issue

17

Start / End Page

3117 / 3127

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Smad Proteins
  • Signal Transduction
  • Receptors, Transforming Growth Factor beta
  • Receptors, Cell Surface
  • Receptor, Transforming Growth Factor-beta Type I
  • Protein Serine-Threonine Kinases
  • Protein Binding
  • Humans
  • Fluorescence Recovery After Photobleaching