R-SMAD

R-SMADs are receptor-regulated SMADs. SMADs are transcription factors 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.^[1]

R-SMADS include SMAD2 and SMAD3 from the TGF-β/Activin/Nodal branch, and SMAD1, SMAD5 and SMAD8 from the BMP/GDP branch of TGF-β signaling.^[1]

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/Activin or Nodal signals.
• SMAD1, SMAD5 and SMAD8 (also known as SMAD9) 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.

See also

• TGF beta signaling pathway

References

Further reading

• Moustakas A, Souchelnytskyi S, Heldin CH (December 2001). "Smad regulation in TGF-beta signal transduction". J. Cell Sci. 114 (Pt 24): 4359–69. doi:10.1242/jcs.114.24.4359. PMID 11792802.

External links

• R-Smad+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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