Phosphoproteome analysis of factor VIIa, Xa, and IIa-dependent signalling defines common and coagulation factor-unique signalling

In preparation 110 Background: Apart from mediating fibrin deposition, the activated coagulation factors(F) VIIa, Xa and thrombin share the common ability to activate protease-activated receptors (PARs), which are generally assumed to mediate critical functions in angiogenesis and smooth and cardiac muscle physiology. The common ability of coagulation factors to activate the same PARs gives rise to the question as to the specificity of coagulation FVIIa, activated FX (FXa) and thrombin-induced engagement of PARs on target cell physiology. Methods and Results: We generated comprehensive descriptions of coagulation factor signal transduction employing peptide-arrays containing 1024 spatially-addressed mammalian kinase substrates. The results clearly define coagulation factor-specific signalling for FVIIa, FXa, and thrombin, in addition to a set of signal transduction pathways common to these coagulation factors. Differences between coagulation factors are especially pronounced in cell cycle regulating pathways. Conclusions: Thus despite the common ability to engage PARs coagulation factors exert highly specific effects on cellular physiology.