Figure 3.

Model of extracellular GRP78 and interacting protein, Cripto, modulation of TGFβ signaling. (A) Transforming growth factor beta (TGFβ) ligand binding to TGFβ receptors (TGFR) leads to activation of genes responsive to Smad2/3 signaling. (B) The 78 kDa glucose regulated protein (GRP78), an ER luminal Ca²⁺-binding chaperone, is secreted upon ER Ca²⁺ depletion. Secreted GRP78 is a co-factor required for Cripto-1 growth factor (Cripto) activation. Cripto activates Src, Ras/Raf/MAPK and PI3K/Akt pathways via a mechanism that remains unknown. (C) Cell surface Cripto/GRP78 interaction is required for Cripto modulation of TGFβ signaling.