Reactome | TGFBR2 recruits TGFBR1

TGFBR2 recruits TGFBR1

Stable Identifier

R-HSA-170846

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane, cytosol

Synonyms

Type II receptor recruits type I receptor

ReviewStatus

4/5

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The protein complex of dimeric TGF-beta-1 with the type II receptor dimer (dimeric TGFB1:TGFBR2 homodimer) recruits the low affinity receptor, type I receptor (TGFBR1), thus forming a hetero-tetrameric receptor bound to the dimeric ligand on the extracellular face of the plasma membrane (TGFB1:TGFBR2:TGFBR1) (Wrana et al. 1992, Moustakas et al. 1993, Franzen et al. 1993). FKBP1A (FKBP12), a peptidyl-prolyl cis-trans isomerase, forms a complex with TGFBR1 and prevents phosphorylation of TGFBR1 by TGFBR2 in the absence of ligand. FKBP1A dissociates from TGFBR1 after it forms a complex with ligand-activated TGFBR2 (Chen et al. 1997). TGFBR1 can homodimerize in the absence of TGFB1 when overexpressed, but under physiological conditions it exists as a monomer on the surface of unstimulated cells. TGFB1-induced dimerization of TGFBR1 is TGFBR2-dependent (Zhang et al. 2010). Also, TGFBR3, a glycoprotein, binds primarily to TGFB2 and facilitates the TGFBR2 binding with its ligand and also its binding with TGFBR1 by bringing ligands in close proximity to TGFBR2 (Lopez-Casillas et al. 1993, Blobe et al. 2001).

Literature References

PubMed ID	Title	Journal	Year
8242743	Cloning of a TGF beta type I receptor that forms a heteromeric complex with the TGF beta type II receptor Franzen, P, ten Dijke, P, Ichijo, H, Yamashita, H, Schulz, P, Heldin, CH, Miyazono, K	Cell	1993
7693660	The transforming growth factor beta receptors types I, II, and III form hetero-oligomeric complexes in the presence of ligand Moustakas, A, Lin, HY, Henis, YI, Plamondon, J, O'Connor-McCourt, MD, Lodish, HF	J Biol Chem	1993
1333888	TGF beta signals through a heteromeric protein kinase receptor complex Wrana, JL, Attisano, L, Carcamo, J, Zentella, A, Doody, J, Laiho, M, Wang, XF, Massague, J	Cell	1992
9233797	Mechanism of TGFbeta receptor inhibition by FKBP12 Chen, YG, Liu, F, Massague, J	EMBO J	1997
20625381	Monomeric type I and type III transforming growth factor-? receptors and their dimerization revealed by single-molecule imaging Zhang, W, Yuan, J, Yang, Y, Xu, L, Wang, Q, Zuo, W, Fang, X, Chen, YG	Cell Res.	2010