Focal Adhesion Kinases in Platelet Function and Thrombosis

The focal adhesion kinase family includes 2 homolog members, FAK and Pyk2 (proline-rich tyrosine kinase 2), primarily known for their roles in nucleated cells as regulators of cytoskeletal dynamics and cell adhesion. FAK and Pyk2 are also expressed in megakaryocytes and platelets and are activated by soluble agonists and on adhesion to the subendothelial matrix. Despite high sequence homology and similar molecular organization, FAK and Pyk2 play different roles in platelet function. Whereas FAK serves mostly as a traditional focal adhesion kinase activated downstream of integrins, Pyk2 coordinates multiple signals from different receptors. FAK, but not Pyk2, is involved in megakaryocyte maturation and platelet production. In circulating platelets, FAK is recruited by integrin αIIbβ3 to regulate hemostasis, whereas it plays minimal roles in thrombosis. By contrast, Pyk2 is implicated in platelet activation and is an important regulator of thrombosis. The direct activation of Pyk2 by calcium ions provides a...