Figure 1.

Diagram of proposed Pi-induced PP2A/Src/DAPK-1/TPM-3 signaling pathway. While hyperphosphorylation of TPM-3 (as the supporting link between TMP-3 and the cytoskeleton) [31] is associated with an enhanced actin stress-fibre formation and works as a protective mechanism in maintaining cell membrane integrity, hypophosphorylation of TPM-3 may result in loss of actin stress-fibres and be associated with membrane blebbing/MV generation from the cells. NB: Pi transporters include Na⁺-Linked PiT-1 (slc20a1) and PiT-2 (slc20a2), with the former the main Pi transporters in endothelial cells (ECs) (described in detail in the Introduction).