Duong L T, Rodan G A
Department of Bone Biology and Osteoporosis Research, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Cell Motil Cytoskeleton. 2000 Nov;47(3):174-88. doi: 10.1002/1097-0169(200011)47:3<174::AID-CM2>3.0.CO;2-N.
Pyk2 is a member of the focal adhesion kinase (FAK) family, highly expressed in the central nervous system and haemopoietic cells. Although Pyk2 is homologous to FAK, its role in signaling pathways was shown to be distinct from that of FAK. We show here that Pyk2 is highly expressed in peritoneal IC-21 macrophage and is tyrosine phosphorylated in response to cell attachment to fibronectin and fibrinogen. Upon IC-21 cell adhesion, Pyk2 tyrosine phosphorylation is inhibited by blocking antibodies to the integrin subunits alpha(M) and beta(2). Furthermore, Pyk2 is rapidly tyrosine phosphorylated in response to ligation of beta(2) integrins by antibodies. In migrating macrophages, Pyk2 localizes to perinuclear regions and to podosomes, where it is clustered with tyrosine phosphorylated proteins. Furthermore, in the podosomal ring structure, which surrounds the central actin core, Pyk2 co-localizes with vinculin, talin, and paxillin. In the podosomes, Pyk2 also co-localizes with the integrin alpha(M)beta(2). Lastly, reduction of Pyk2 expression in macrophages leads to inhibition of cell migration. We propose that Pyk2 is functionally linked to the formation of podosomes where it mediates the integrin-cytoskeleton interface and regulates cell spreading and migration.
Pyk2是粘着斑激酶（FAK）家族的成员，在中枢神经系统和造血细胞中高度表达。尽管Pyk2与FAK同源，但其在信号通路中的作用与FAK不同。我们在此表明，Pyk2在腹膜IC-21巨噬细胞中高度表达，并在细胞附着于纤连蛋白和纤维蛋白原时发生酪氨酸磷酸化。在IC-21细胞粘附时，针对整合素α(M)和β(2)亚基的阻断抗体可抑制Pyk2酪氨酸磷酸化。此外，抗体介导β(2)整合素连接可使Pyk2迅速发生酪氨酸磷酸化。在迁移的巨噬细胞中，Pyk2定位于核周区域和足体，在那里它与酪氨酸磷酸化蛋白聚集在一起。此外，在围绕中央肌动蛋白核心的足体环结构中，Pyk2与纽蛋白、踝蛋白和桩蛋白共定位。在足体中，Pyk2也与整合素α(M)β(2)共定位。最后，巨噬细胞中Pyk2表达的降低导致细胞迁移受到抑制。我们提出，Pyk2在功能上与足体的形成相关联，在足体中它介导整合素-细胞骨架界面并调节细胞铺展和迁移。
