Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis.
Focal adhesion kinase and its signaling pathways in cell migration and angiogenesis.
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DOI：
10.1016/j.addr.2010.11.001
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发表时间：
2011-07-18
影响因子：
16.1
通讯作者：
Guan, Jun-Lin
中科院分区：
文献类型：
--
作者：
Zhao, Xiaofeng;Guan, Jun-Lin
Focal adhesion kinase （FAK）是一种细胞质酪氨酸激酶，在整合素介导的信号转导中起关键作用，也参与其他细胞表面受体的信号传导。在整合素介导的细胞粘附中，FAK通过破坏其氨基末端FERM结构域和中央激酶结构域之间的自抑制性分子内相互作用而被激活。活化的FAK与Src家族激酶形成复合物，通过磷酸化其他蛋白启动多种下游信号通路，调节不同的细胞功能。发现了多种下游信号通路介导FAK调节各种正常细胞和癌细胞的迁移。在培养细胞和条件FAK敲除小鼠模型中进行的广泛研究表明，FAK在胚胎发育和癌症进展期间的血管生成中起着关键作用。最近的研究也揭示了FAK在内皮细胞和成纤维细胞中的激酶非依赖性功能。与其在细胞迁移和血管生成中的作用一致，在多种人类癌症中发现了FAK的表达增加和/或激活。因此，FAK激酶活性的小分子抑制剂以及针对FAK潜在的激酶非依赖性功能的新疗法的未来发展是治疗转移性癌症和其他疾病的有希望的治疗方法。
Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays critical roles in integrin-mediated signal transductions and also participates in signaling by other cell surface receptors. In integrin-mediated cell adhesion, FAK is activated via disruption of an auto-inhibitory intra-molecular interaction between its amino terminal FERM domain and the central kinase domain. The activated FAK forms a complex with Src family kinases, which initiates multiple downstream signaling pathways through phosphorylation of other proteins to regulate different cellular functions. Multiple downstream signaling pathways are identified to mediate FAK regulation of migration of various normal and cancer cells. Extensive studies in cultured cells as well as conditional FAK knockout mouse models indicated a critical role of FAK in angiogenesis during embryonic development and cancer progression. More recent studies also revealed kinase-independent functions for FAK in endothelial cells and fibroblasts. Consistent with its roles in cell migration and angiogenesis, increased expression and/or activation of FAK are found in a variety of human cancers. Therefore, small molecular inhibitors for FAK kinase activity as well as future development of novel therapies targeting the potentially kinase-independent functions of FAK are promising treatments for metastatic cancer as well as other diseases.
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影响因子：
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