TGF-β Superfamily Receptors


The cell surface receptors of TGF beta (TGF-β) superfamily are classified into either type I receptors, type II receptors and co-receptors.

In mammals, there are seven type I TGF-β superfamily receptors and they are named activing receptor like kinases (ALK) 1-7 in TGF-β superfamily. The ALKs’ molecular weights are approximately 55 kD. They are serine/threonine kinases with relatively short extracellular domains. A 30 amino acid domain formed the GS domain of cytoplasmic domain of the type I receptors. The type I receptors are activated through phosphorylation of the GS domain by the TGF-β superfamily type II receptors. The kinase domain which phosphorylates its substrates on serine is in downstream of the GS domain.

There are five type II receptors in the TGF-β superfamily, including BMP type II receptor (BMPRII), Activin type II receptor (ActRII), Activin type II receptor B (ActRIIB), the TGF-β type II receptor (TβRII), and anti-Müllerian hormone receptor (AMHR). These receptors are approximately 70 kDa. They are serine/threonine kinases with short extracellular domains, too. They autophosphorylate and phosphorylate the type I receptors on serines and threonines as above described. There are two serines in the regulatory region of the type II receptors promoting or inhibiting the activity of the type II receptors by phosphorylation.

In the TGF-β superfamily, there are also co-receptors, including the type III TGF-β receptor (TβRIII), DRAGON (RGMb), RGMa, endoglin and hemojuvelin/HFE2 (RGMc).

 

The TGF-β superfamily transmembrane receptors, ligands, and Smads.

Type I Receptors

Ligands

Receptor Smads

ALK1

TGF-β1, TGF-β3, BMP-9, Activin A

Smads 1/5/8

ALK2

Activin A, MIS, BMP-7, BMP-6

Smads 1/5/8

ALK3

BMP-2, BMP-4, BMP-6, BMP-7

Smads 1/5/8

ALK4

Activin A, GDF-1, GDF-11, Nodal

Smads 2/3

ALK5

TGF- β1, TGF- β2, TGF- β3

Smads 2/3

ALK6

BMP-2, BMP-4, BMP-6, BMP-7, GDF-5, GDF-6, GDF-9b, MIS

Smads 1/5/8

ALK7

Nodal

Smads 2/3

Type II Receptors

Ligands

TβRII

TGF-β1, TGF-β2, TGF-β3

Activin RII

Activin A, BMP-2, BMP-6, BMP-7, GDF-1, GDF-5, GDF-8, GDF-9b, GDF-11, Inhibin A, Inhibin B

Activin RIIb

Activin A, BMP-2, BMP-6, BMP-7, GDF-5, GDF-8, GDF-11, Inhibin A, Inhibin B, Nodal

BMPRII

BMP-2, BMP-4, BMP-6, BMP-7, GDF-5, GDF-6, GDF-9b

MISRII

MIS

Co-Receptors

Ligands

TβRIII

TGF-β1, TGF-β2, TGF-β3, BMP-2, BMP-4, BMP-7, GDF-5

Endoglin

TGF-β1, TGF-β3, Activin A, BMP-2, BMP-7, BMP-9

 

 

BMP Modulator
GDNF Family Signaling Molecules
TGF-beta Family Modulators

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