R-SMAD

R-SMAD stands for receptor-regulated SMAD. Smads are transcription factors that transduce extracellular TGF-ß superfamily ligand signaling from cell membrane bound TGF-ß receptors into the nucleus where they activate transcription TGF-ß target genes. R-SMADS are directly phosphorylated on their c-terminus by type 1 TGF-ß receptors through their intracellular kinase domain, leading to r-SMAD activation. R-SMADS include SMAD2 and SMAD3 from the TGF-ß/Activin/Nodal branch, and SMAD1, SMAD5 and SMAD8 from the BMP/GDP branch of TGF-ß signaling.

R-Smads include SMAD1, SMAD2, SMAD3, SMAD5, and SMAD8.

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 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-ß receptors for degradation.