I-Smad competes with R-Smad1/5/8 for type I receptor

I-SMADs reside in the nucleus presumably to be sequestered from the BMP2:receptor complex and thus avoid inappropriate silencing of the signalling pathway. Upon activation of the signalling pathway, I-SMADs exit the nucleus and are recruited to the signalling BMP2:receptor complex. I-SMADs directly bind to the so-called L45 loop of the type I receptor, the site of binding of R-SMADs. Thus, I-SMADs competitively inhibit the activation/phosphorylation of R-SMADs.

I-SMADs位于细胞核内，据推测是为了与BMP2:受体复合物隔离，从而避免信号通路的不当沉默。在信号通路的激活过程中，I-SMADs脱离细胞核，并被招募至BMP2:受体复合物。I-SMADs直接结合至I型受体的所谓L45环，这是R-SMADs的结合位点。因此，I-SMADs可通过竞争性抑制R-SMADs的激活/磷酸化来抑制其活性。