FIGURE 5.

Schematic overview. A, in normoxia BMP binds its receptor, activating intracellular SMAD phosphorylation pathways that lead to activation of the hepcidin promoter through its BRE. B, in hypoxia, HIF-dependent transcription of TMPRSS6 leads to cleavage and shedding of the BMPR co-receptor, HJV, from the cell membrane leading to reduced BMP/BRE signaling. In addition, cleavage of HJV in the Golgi apparatus by furin leads to increased secretion of soluble HJV, which acts as a “decoy receptor” that synergizes with reduced co-receptor levels to further reduce signaling to the BRE.