From the Department of Biology and Biotechnology, University of Pavia, Italy.
Arterioscler Thromb Vasc Biol. 2019 May;39(5):857-868. doi: 10.1161/ATVBAHA.118.311787.
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 connection between GPCRs (G-protein coupled receptors) and Src family kinases. In this review, we provide the comprehensive overview of >20 years of investigations on the role and regulation of focal adhesion kinases in blood platelets, highlighting common and distinctive features of FAK and Pyk2 in hemostasis and thrombosis.
黏着斑激酶家族包括 2 个同源成员，黏着斑激酶（FAK）和富含脯氨酸的酪氨酸激酶 2（Pyk2），它们主要作为核细胞中细胞骨架动态和细胞黏附的调节剂发挥作用。FAK 和 Pyk2 也在巨核细胞和血小板中表达，并在与内皮下基质黏附时被可溶性激动剂激活。尽管具有高度的序列同源性和相似的分子结构，但 FAK 和 Pyk2 在血小板功能中发挥着不同的作用。FAK 主要作为整合素下游的传统黏着斑激酶被激活，而 Pyk2 则协调来自不同受体的多种信号。FAK 而不是 Pyk2 参与巨核细胞成熟和血小板生成。在循环血小板中，FAK 通过整合素 αIIbβ3 募集以调节止血，而在血栓形成中作用较小。相比之下，Pyk2 参与血小板激活，是血栓形成的重要调节剂。钙离子对 Pyk2 的直接激活提供了 G 蛋白偶联受体（GPCRs）和 Src 家族激酶之间的联系。在这篇综述中，我们全面概述了 20 多年来对黏着斑激酶在血小板中的作用和调节的研究，强调了 FAK 和 Pyk2 在止血和血栓形成中的共同和独特特征。
