Intracellular signaling in platelets

Purpose of review Over the past few years, a large portion of platelet research has focused on intracellular signalling events that contribute to stable platelet adhesion and aggregation. Recent findings Studies of knockout mice have suggested critical roles fro several previously unappreciated signaling molecules including phosphatidylinositol 3-kinase, the exchange factor CalDAG-GEFI, and the small GTPase Rap1b. These proteins may function to remodel the platelet cytoskeleton and therby regulate both adhesion and aggregation. The abundant cytoskeletal protein talin appears to be a key regulator of the platelet integrin alpha IIb beta 3. Recent evidence suggests that talin binding to the cytoplasmic tail of beta(3) promotes integrin oligomerization, thereby increasing the binding avidity the alpha IIb beta 3 complex for fibrinogen. Summary The identification of platelet signalling pathways not only has clinical implications for diagnosis, but perhaps more importantly for rationale drug design. Aspirin, dipryidamole (Persantine), and thienopyridines (ticlopidine and clopidogrl) are all examples of agents that specifically target discrete platelet signaling pathways. These drugs have been proven to be beneficial in the treatment of cardiovascular disease. Novel agents that target newly identified signaling pathways hold promise of greater specificity and efficacy.