The ability of signaling elements to move from one compartment to another could mean that more than one pathway might be triggered by a given stimulus. Moreover, the coagulation pathway can become activated by release of cell signaling molecules as well as, for example, the activation of the endothelial monocyte-complement pathway. Activated platelets express the collagen receptor, GPVI. This is the platelet receptor for collagen and a crucial signaling molecule in the platelet coagulation pathway (Figure 4.3). As well, the GPVI-collagen induced platelet-endothelial cell interaction plays a role in hemostasis activated by vascular injury because of one or more of a number of procoagulant activities on the endothelium. The resulting interaction of both platelets and endothelial cells is likely to play an important role in the pathobiology of various cardiovascular disease states.
Therefore, it is important to understand the signaling pathways that are activated by the interaction of the GPVI and collagen receptors. The GPVI-coupled signaling pathway plays a major role in platelet adhesion and thrombus formation under static conditions. GPVI is a member of the immunoglobulin superfamily and contains two immunoreceptor tyrosine-based activation motifs in its cytoplasmic tail. Upon stimulation of platelet GPVI, phosphorylations are induced on tyrosine residues in the tyrosine-based activation motifs leading to the recruitment of kinases including PLC. This leads to calcium influx into platelets and activation of PKC. The PKC substrate is the GPVI associated with phospholipase Cγ (PLCγ), a fact that is the target of a number of pharmacological inhibitors of platelet activation.
It is important to note that the activation of all these biochemical and signaling pathways is cell-type specific and care should be taken in choosing an appropriate system . It could also be useful to identify commonalities of receptor signaling in different systems. At this point, comprehensive theoretical models of receptor signaling pathways might provide information at a system level that may not be arrived at experimentally. d2c66b5586