p-2S-SMAD1/5/8:SMAD4 p-2S-SMAD1/5/8:SMAD4 The phospho-R-Smad1/5/8:Co-Smad transfers to the nucleus Authored: Huminiecki, L, Moustakas, A, 2007-11-07 10:22:00 Pubmed11509558 Pubmed12592392 Pubmed12821673 Reactome Database ID Release 43201472 Reactome, http://www.reactome.org ReactomeREACT_12067 Reviewed: Heldin, CH, 2007--1-1- The phosphorylated-r-SMAD1/5/8:Co-SMAD complex rapidly translocates to the nucleus where it binds directly to DNA and interacts with a plethora of transcription co-factors. Regulation of target gene expression can be either positive or negative. A classic example of a target gene of the pathway are the genes encoding for i-SMADs. Thus, BMP2/SMAD signalling induces the expression of the negative regulators of the pathway (a negative feedback loop).