R-SMAD
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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 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
References
- ^ a b Wharton K, Derynck R (November 2009). "TGFbeta family signaling: novel insights in development and disease". Development. 136 (22): 3691–7. doi:10.1242/dev.040584. PMID 19855012.
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. PMID 11792802.
External links
- R-Smad+Proteins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)