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

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....

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Autores principales: Pomeraniec, Leslie, Hector-Greene, Melissa, Ehrlich, Marcelo, Blobe, Gerard C., Henis, Yoav I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551323/
https://www.ncbi.nlm.nih.gov/pubmed/26157163
http://dx.doi.org/10.1091/mbc.E15-02-0069
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author Pomeraniec, Leslie
Hector-Greene, Melissa
Ehrlich, Marcelo
Blobe, Gerard C.
Henis, Yoav I.
author_facet Pomeraniec, Leslie
Hector-Greene, Melissa
Ehrlich, Marcelo
Blobe, Gerard C.
Henis, Yoav I.
author_sort Pomeraniec, Leslie
collection PubMed
description 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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spelling pubmed-45513232015-11-16 Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin Pomeraniec, Leslie Hector-Greene, Melissa Ehrlich, Marcelo Blobe, Gerard C. Henis, Yoav I. Mol Biol Cell Articles 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. The American Society for Cell Biology 2015-09-01 /pmc/articles/PMC4551323/ /pubmed/26157163 http://dx.doi.org/10.1091/mbc.E15-02-0069 Text en © 2015 Pomeraniec et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Pomeraniec, Leslie
Hector-Greene, Melissa
Ehrlich, Marcelo
Blobe, Gerard C.
Henis, Yoav I.
Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin
title Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin
title_full Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin
title_fullStr Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin
title_full_unstemmed Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin
title_short Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin
title_sort regulation of tgf-β receptor hetero-oligomerization and signaling by endoglin
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4551323/
https://www.ncbi.nlm.nih.gov/pubmed/26157163
http://dx.doi.org/10.1091/mbc.E15-02-0069
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