R-SMADs are receptor-regulated SMADs. SMADs are

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...

s that transduce extracellular TGF-β superfamily ligand signaling from cell membrane bound TGF-β receptors into the nucleus where they activate transcription TGF-β target genes. R-SMADS are directly phosphorylated on their c-terminus by type 1 TGF-β receptors through their intracellular kinase domain, leading to R-SMAD activation. R-SMADS include

SMAD2 Mothers against decapentaplegic homolog 2, also known as SMAD family member 2 or SMAD2, is a protein that in humans is encoded by the ''SMAD2'' gene. MAD homolog 2 belongs to the SMAD, a family of proteins similar to the gene products of the ''Dr ...

and SMAD3 from the TGF-β/Activin/ Nodal branch, and

SMAD1 Mothers against decapentaplegic homolog 1 also known as SMAD family member 1 or SMAD1 is a protein that in humans is encoded by the ''SMAD1'' gene. Nomenclature SMAD1 belongs to the SMAD (protein), SMAD, a family of proteins similar to the gene p ...

, SMAD5 and SMAD9 from the BMP/GDP branch of TGF-β signaling. In response to signals by the TGF-β superfamily of

ligand In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's el ...

s these proteins associate with receptor

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

s and are phosphorylated at an SSXS motif at their extreme

C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, carboxy tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein Proteins are large biomolecules and macromolecules that comp ...

. These proteins then typically bind to the common mediator Smad or co-SMAD SMAD4. Smad complexes then accumulate in the

cell nucleus The cell nucleus (; : nuclei) is a membrane-bound organelle found in eukaryote, eukaryotic cell (biology), cells. Eukaryotic cells usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have #Anucleated_cells, ...

where they regulate transcription of specific target genes: * SMAD2 and SMAD3 are activated in response to TGF-β/ Activin or Nodal signals. * SMAD1, SMAD5 and SMAD9 (also known as SMAD8) are activated in response to BMPs bone morphogenetic protein or GDP signals. SMAD6 and SMAD7 may be referred to as I-SMADs (inhibitory SMADS), which form trimers with R-SMADS and block their ability to induce gene transcription by competing with R-SMADs for receptor binding and by marking TGF-β receptors for degradation.

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External links

* Developmental genes and proteins SMAD (protein) {{molecular-cell-biology-stub

See also

References

Further reading

External links