Fig. 8. Model for CaM KIV-mediated inhibition of BMP signaling (details in text). Nuclear component of an active BMP signal in which the Smad complex is linked to a hematopoietic-specific transcription factor (purple box) by the coactivator CBP. CaM KIV inhibits interactions between the Smad/CBP complex and other transcriptional components by activating a downstream substrate such as CREB. Endogenous levels of CaM KIV activity partially repress BMP-mediated transcription in ectodermal cells, leading to expression of a secreted protein that promotes erythroid fate and survival. Abnormally high levels of this gene product lead to excessive myeloid fate, abnormally low levels lead to apoptosis of RBCs.