TGF-beta receptor family explained

See also: TGF beta receptor and TGFβ signaling pathway.

The transforming growth factor beta (TGFβ) receptors are a family of serine/threonine kinase receptors involved in TGF beta signaling pathway. These receptors bind growth factor and cytokine signaling proteins in the TGF-beta family such as TGFβs (TGFβ1, TGFβ2, TGFβ3), bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), activin and inhibin, myostatin, anti-Müllerian hormone (AMH), and NODAL.^[1]

TGFβ family receptors

TGFβ family receptors are grouped into three types, type I, type II, and type III. There are seven type I receptors, termed the activin-like receptors (ALK1–7), five type II receptors, and one type III receptor, for a total of 13 TGFβ superfamily receptors.^{[2] [3]} In the transduction pathway, ligand-bound type II receptors activate type I receptors by phosphorylation, which then autophosphorylate and bind SMAD.^[4] The Type I receptors have a glycine-serine (GS, or TTSGSGSG) repeat motif of around 30 AA, a target of type II activity. At least three, and perhaps four to five of the serines and threonines in the GS domain, must be phosphorylated to fully activate TbetaR-1.^[5]

Type I

• ALK1 (ACVRL1)
• ALK2 (ACVR1A)
• ALK3 (BMPR1A)
• ALK4 (ACVR1B)
• ALK5 (TGFβR1)
• ALK6 (BMPR1B)
• ALK7 (ACVR1C)

Type II

• TGFβR2
• BMPR2
• ACVR2A
• ACVR2B
• AMHR2 (AMHR)

Type III

Unlike the Type I and II receptors which are kinases, TGFBR3 has a Zona pellucida-like domain. Its core domain binds TGF-beta family ligands and its heparan sulfate chains bind bFGF. It acts as a reservoir of ligand for TGF-beta receptors.^{[6] [7]}

• TGFβR3 (β-glycan)

Notes and References

1. Web site: Prosite Documentation PDOC00223 . 2006-07-01 . https://web.archive.org/web/20110525160027/http://www.expasy.org/cgi-bin/nicedoc.pl?PS00250. dead . 2011-05-25.
2. Book: Steven J. . Fliesler . Oleg G. . Kisselev . vanc . Signal Transduction in the Retina. 26 December 2007. CRC Press. 978-1-4200-0716-9. 273–.
3. Book: Thiriet, Marc . vanc . Signaling at the Cell Surface in the Circulatory and Ventilatory Systems. 14 December 2011. Springer Science & Business Media. 978-1-4614-1991-4. 666–.
4. Wrana JL, Attisano L, Cárcamo J, etal . TGF beta signals through a heteromeric protein kinase receptor complex . Cell . 71 . 6 . 1003–14 . December 1992 . 1333888 . 10.1016/0092-8674(92)90395-S. 54397586 .
5. Huse . M . Muir . TW . Xu . L . Chen . YG . Kuriyan . J . Massagué . J . The TGF beta receptor activation process: an inhibitor- to substrate-binding switch. . Molecular Cell . September 2001 . 8 . 3 . 671–82 . 11583628. 10.1016/S1097-2765(01)00332-X . free .
6. Andres JL, Stanley K, etal . Membrane-anchored and soluble forms of betaglycan, a polymorphic proteoglycan that binds transforming growth factor-beta . J. Cell Biol. . 1989 . 109 . 6 (Pt 1) . 3137–3145 . 2592419 . 10.1083/jcb.109.6.3137 . 2115961.
7. Andres JL, DeFalcis D, etal . Binding of two growth factor families to separate domains of the proteoglycan betaglycan . J. Biol. Chem. . 1992 . 267 . 9 . 5927–5930 . 10.1016/S0021-9258(18)42643-9 . 1556106 . free .