Reactome | Signaling by TGFBR3

Signaling by TGFBR3

Stable Identifier

R-HSA-9839373

Type

Pathway

Species

Homo sapiens

ReviewStatus

3/5

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TGFBR3, also known as betaglycan, is a member of the proteoglycan family (Zhang et al., 2020) and plays a key role in regulating TGF-beta receptor-mediated signaling (Esparza-Lopez et al., 2001, Blobe et al., 2001) as well as TGF-beta-independent signaling (Wiater et al.,2003, Andres et al., 1992). TGFBR3 is expressed in abundance in normal cells (Wang et al, 1991) and is known to be down-regulated in multiple cancers due to its function as a tumor suppressor (Zhang et al.,2020, Fang et al.,2020, Cook et al.,2019). TGFBR3 is a transmembrane protein but lacks kinase activity in its cytoplasmic domain (López-Casillas et al.,1991). TGFBR3 primarily works as a co-receptor for different signaling pathways and can either facilitate or inhibit them (Wiater et al.,2003, Andres et al., 1992, Esparza-Lopez et al., 2001). TGFBR3 binds to TGF-beta ligands, facilitates their presentation to the TGFBR2 receptor, and helps in complex formation between TGFBR2 and TGFBR1 (Esparza-Lopez et al., 2001, Blobe et al., 2001). TGFBR3 also facilitates FGF:FGFR receptor complex stability and functions in FGFR1-mediated signaling as a co-receptor (Andres et al., 1992). TGBFR3 regulates signaling by other TGF-beta family members, including BMP2/7 and Activin (Wiater et al.,2003). Thus, TGFBR3 is involved in normal cell signaling and plays an important role in cancer, inflammatory diseases (Santiago et al, 2020), and Alzheimer's (Song et al., 2022).

Literature References

PubMed ID	Title	Journal	Year
12493742	Inhibin is an antagonist of bone morphogenetic protein signaling Wiater, E, Vale, W	J Biol Chem	2003
31409900	Betaglycan drives the mesenchymal stromal cell osteogenic program and prostate cancer-induced osteogenesis Stewart, PA, Cook, LM, Lynch, CC, McGuire, JJ, Frieling, JS, Nerlakanti, N, Cleveland, JL, Burger, KL	Oncogene	2019
35310542	Promoter Hypomethylation of TGFBR3 as a Risk Factor of Alzheimer's Disease: An Integrated Epigenomic-Transcriptomic Analysis Yang, J, Song, H, Yu, W	Front Cell Dev Biol	2021
8391934	Betaglycan presents ligand to the TGF beta signaling receptor Wrana, JL, López-Casillas, F, Massagué, J	Cell	1993
21167215	The type III TGF-β receptor betaglycan transmembrane-cytoplasmic domain fragment is stable after ectodomain cleavage and is a substrate of the intramembrane protease γ-secretase Wells, RG, Blair, CR, Stone, JB	Biochim Biophys Acta	2011
14672946	The shedding of betaglycan is regulated by pervanadate and mediated by membrane type matrix metalloprotease-1 Arribas, J, Velasco-Loyden, G, López-Casillas, F	J Biol Chem	2004
15147205	Mechanism of gamma-secretase cleavage activation: is gamma-secretase regulated through autoinhibition involving the presenilin-1 exon 9 loop? Ye, X, Ghanekar, SV, Greenberg, BD, Tian, G, Scott, CW, Sobotka-Briner, C, Knappenberger, KS	Biochemistry	2004
20445084	Structural investigation of the C-terminal catalytic fragment of presenilin 1 Ghoshdastider, U, Gottstein, D, Ikeya, T, Schneider, B, Dötsch, V, Mlynarczyk, K, Filipek, S, Löhr, F, Güntert, P, Pulawski, W, Bernhard, F, Sobhanifar, S, Kolinski, M	Proc. Natl. Acad. Sci. U.S.A.	2010
12399463	Betaglycan expression is transcriptionally up-regulated during skeletal muscle differentiation. Cloning of murine betaglycan gene promoter and its modulation by MyoD, retinoic acid, and transforming growth factor-beta Cabello-Verrugio, C, Mendoza, V, Osses, N, Gonzalez-Nunez, G, Ponce-Castaneda, MV, Brandan, E, Riquelme, C, López-Casillas, F, Perez-Kato, Y, Esparza-Lopez, J, Troncoso, V	J Biol Chem	2003
8106553	Betaglycan can act as a dual modulator of TGF-beta access to signaling receptors: mapping of ligand binding and GAG attachment sites Payne, HM, López-Casillas, F, Massagué, J, Andres, JL	J Cell Biol	1994
11278442	Ligand binding and functional properties of betaglycan, a co-receptor of the transforming growth factor-beta superfamily. Specialized binding regions for transforming growth factor-beta and inhibin A Vilchis-Landeros, MM, López-Casillas, F, Montiel, JL, Esparza-Lopez, J, Okadome, T, Miyazono, K	J Biol Chem	2001
1556106	Binding of two growth factor families to separate domains of the proteoglycan betaglycan DeFalcis, D, Noda, M, Massagué, J, Andres, JL	J Biol Chem	1992
21871877	The cytoplasmic domain of TGFβR3 through its interaction with the scaffolding protein, GIPC, directs epicardial cell behavior Barnett, JV, Camenisch, TD, Craig, E, Czirok, A, Hill, CR, Austin, AF, Brown, CB, Love, JD, Soslow, JH, Sánchez, NS	Dev Biol	2011
24216509	Type III TGF-β receptor promotes FGF2-mediated neuronal differentiation in neuroblastoma Mythreye, K, Blobe, GC, Armstrong, MB, Gaviglio, AL, Tewari, AK, Knelson, EH	J Clin Invest	2013
32583064	Role of glycosylation in TGF-β signaling and epithelial-to-mesenchymal transition in cancer Zhang, J, Wuhrer, M, Ten Dijke, P, Zhang, T	Protein Cell	2021
33149723	Transforming Growth Factor Beta Receptor 3 Haplotypes in Sickle Cell Disease Are Associated with Lipid Profile and Clinical Manifestations Gonçalves, MS, Fonseca, CA, Santiago, RP, Aleluia, MM, Yahouédéhou, SCMA, Figueiredo, CVB, Nascimento, VML, Guarda, CC, Fiuza, LM, Oliveira, RM, Rocha, LC, Carvalho, SP	Mediators Inflamm	2020
11546783	A novel mechanism for regulating transforming growth factor beta (TGF-beta) signaling. Functional modulation of type III TGF-beta receptor expression through interaction with the PDZ domain protein, GIPC Lodish, HF, Blobe, GC, How, T, Liu, X, Fang, SJ	J Biol Chem	2001
11323414	Functional roles for the cytoplasmic domain of the type III transforming growth factor beta receptor in regulating transforming growth factor beta signaling Lodish, HF, Schiemann, WP, Blobe, GC, Pepin, MC, Moustakas, A, O'Connor-McCourt, MD, Beauchemin, M	J Biol Chem	2001