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. Author manuscript; available in PMC: 2012 Nov 7.
Published in final edited form as: Trends Neurosci. 2011 Feb 25;34(4):198–209. doi: 10.1016/j.tins.2011.01.005

Figure 1. Pathways for protein C activation and expression of anticoagulant activity.

Figure 1

The endothelial cell receptors, thrombomodulin (TM) and EPCR, are required for efficient activation of protein C by alpha-thrombin (IIa). Dissociation of APC from EPCR allows for the expression of APC’s anticoagulant activity, whereas retention of APC bound to EPCR allows APC to express multiple direct cellular activities in the endothelium (see Figure 3a). APC conveys its anticoagulant activity when bound to cell membrane surfaces by cleaving the activated cofactors Va (fVa) and VIIIa (fVIIIa) to yield the inactivated cofactors, fVi and fVIIIi. Various proteins such as plasma protein S and factor V, high density lipoprotein particles, lipids (e.g., negatively charged phosphatidyl serine and cardiolipin, phosphatidyl ethanolamine) and certain glycosphingolipids (e.g., glycosyl ceramide, lactosyl ceramide, etc) provide APC-cofactor activities that accelerate proteolysis of factors Va and VIIIa by APC (not shown). Figure adapted from a review article originally published by L. Mosnier, B. Zlokovic and J.H. Griffin (2007) The cytoprotective protein C pathway Blood, 109, 3161-3172 [28].