TY - JOUR
T1 - Regulation of TGF-β receptor hetero-oligomerization and signaling by endoglin
AU - Pomeraniec, Leslie
AU - Hector-Greene, Melissa
AU - Ehrlich, Marcelo
AU - Blobe, Gerard C.
AU - Henis, Yoav I.
N1 - Publisher Copyright:
© 2015 Pomeraniec et al.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84940417059&partnerID=8YFLogxK
U2 - 10.1091/mbc.E15-02-0069
DO - 10.1091/mbc.E15-02-0069
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AN - SCOPUS:84940417059
SN - 1059-1524
VL - 26
SP - 3117
EP - 3127
JO - Molecular Biology of the Cell
JF - Molecular Biology of the Cell
IS - 17
ER -
