In response to signals by the TGF-β superfamily of ligands these proteins associate with receptor kinases and are phosphorylated at an SSXS motif at their extreme C-terminus. These proteins then typically bind to the common mediator Smad or co-SMAD SMAD4.
Smad complexes then accumulate in the cell nucleus where they regulate transcription of specific target genes:
- SMAD2 and SMAD3 are activated in response to TGF-β or Activin signals.
- SMAD1, SMAD5 and SMAD9 are activated in response to BMP or bone morphogenetic protein signals.
Transcription factors and intracellular receptors
|(1) Basic domains|
|(2) Zinc finger|
|(4) β-Scaffold factors with|
minor groove contacts
| (0) Other|
Cell signaling: TGF beta signaling pathway
|TGF beta superfamily of ligands||TGF beta family (TGF-β1, TGF-β2, TGF-β3)|
Bone morphogenetic proteins (BMP2, BMP3, BMP4, BMP5, BMP6, BMP7, BMP8a, BMP8b, BMP10 , BMP15)
Growth differentiation factors (GDF1, GDF2, GDF3, GDF5, GDF6, GDF7, Myostatin/GDF8, GDF9, GDF10, GDF11, GDF15)
Other (Activin A and B/Inhibin A and B, Anti-müllerian hormone, Nodal)
|TGF beta receptors||TGFBR1: Activin type 1 receptors (ACVR1, ACVR1B, ACVR1C) - ACVRL1 - BMPR1 (BMPR1A - BMPR1B) |
TGFBR2: Activin type 2 receptors (ACVR2A, ACVR2B) - AMHR2 - BMPR2
|Transducers/SMAD||R-SMAD (SMAD1, SMAD2, SMAD3, SMAD5, SMAD9) - I-SMAD (SMAD6, SMAD7) - SMAD4|
|Ligand Inhibitors||Cerberus - Chordin - DAN - Decorin - Follistatin - Gremlin - Lefty - LTBP1 - Noggin - THBS1|
|Coreceptors||BAMBI - Cripto|
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