Cellular effects and signalling pathways activated by the anti-coagulant factor, protein S, in vascular cells protein...

The anticoagulant factor protein S is a secreted vitamin K-dependent gamma-carboxylated protein that is mainly synthesised in the liver but is also made by endothelial cells and megakaryocytes in culture. In previous studies we have shown that protein S acts as a mitogen for cultured human vascular smooth muscle cells. The synthesis and secretion of protein S by endothelial cells suggests that in addition to its role in the coagulation cascade, protein S may be an important autocrine factor implicated in the pathophysiology of the vascular system. The effects of protein S on hVSMC proliferation, migration and survival are discussed. The activation of the components of the MAP kinase pathway, ERK1/2, JNK/SAPK and p38 is also summarised. Binding and chemical cross-linking experiments provided evidence for the existence of a cell surface protein S receptor(s). By virtue of its many cellular effects, it is suggested here that the anticoagulant factor protein S plays an important role in the pathophysiology of the vasculature.