Paxillin: a crossroad in pathological cell migration.
Paxillin: a crossroad in pathological cell migration.
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DOI：
10.1186/s13045-017-0418-y
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发表时间：
2017-02-18
影响因子：
28.5
通讯作者：
López E
中科院分区：
文献类型：
--
作者：
López-Colomé AM;Lee-Rivera I;Benavides-Hidalgo R;López E
Paxilllin是一种多功能和多结构域的粘着斑衔接蛋白，当在特定的Tyr和Ser残基上磷酸化时，其通过募集参与细胞运动和迁移的结构和信号分子而在粘着斑中起到重要的支架作用。当整合素与细胞外基质结合时，桩蛋白在Tyr 31、Tyr 118、Ser 188和Ser 190处被磷酸化，激活促进细胞迁移的众多信号级联，表明粘附动力学的调节是在信号机制的复杂显示的控制下。其中，由细胞外调节激酶（ERK）介导的丝氨酸106、231和290的磷酸化以及磷酸酶PEST与桩蛋白的结合诱导的来自粘着斑的桩蛋白分解已被证明在细胞迁移中起关键作用。Paxillin还通过募集GEF、GAP和GIT至粘着斑来协调信号分子（包括Cdc 42、Rac 1和RhoA GTP酶）的时空激活。作为细胞运动调节的主要参与者，桩蛋白在特定组织和发育阶段发挥独特的作用，并参与免疫应答、上皮形态发生和胚胎发育。重要的是，桩蛋白也是病理条件，包括氧化应激，炎症，内皮细胞屏障功能障碍，以及癌症发展和转移的重要参与者。本文的在线版本（doi：10.1186/s13045-017-0418-y）包含补充材料，可供授权用户使用。
Paxilllin is a multifunctional and multidomain focal adhesion adapter protein which serves an important scaffolding role at focal adhesions by recruiting structural and signaling molecules involved in cell movement and migration, when phosphorylated on specific Tyr and Ser residues. Upon integrin engagement with extracellular matrix, paxillin is phosphorylated at Tyr31, Tyr118, Ser188, and Ser190, activating numerous signaling cascades which promote cell migration, indicating that the regulation of adhesion dynamics is under the control of a complex display of signaling mechanisms. Among them, paxillin disassembly from focal adhesions induced by extracellular regulated kinase (ERK)-mediated phosphorylation of serines 106, 231, and 290 as well as the binding of the phosphatase PEST to paxillin have been shown to play a key role in cell migration. Paxillin also coordinates the spatiotemporal activation of signaling molecules, including Cdc42, Rac1, and RhoA GTPases, by recruiting GEFs, GAPs, and GITs to focal adhesions. As a major participant in the regulation of cell movement, paxillin plays distinct roles in specific tissues and developmental stages and is involved in immune response, epithelial morphogenesis, and embryonic development. Importantly, paxillin is also an essential player in pathological conditions including oxidative stress, inflammation, endothelial cell barrier dysfunction, and cancer development and metastasis. The online version of this article (doi:10.1186/s13045-017-0418-y) contains supplementary material, which is available to authorized users.