EphrinA1-induced cytoskeletal re-organization requires FAK and p130cas
EphrinA1-induced cytoskeletal re-organization requires FAK and p130cas
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DOI：
10.1038/ncb823
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发表时间：
2002-08-01
影响因子：
21.3
通讯作者：
Hunter, T
中科院分区：
文献类型：
--
作者：
Carter, N;Nakamoto, T;Hunter, T
Ephrin和Eph受体参与轴突导向和细胞形态发生。Ephrin和Eph受体之间的相互作用通过细胞骨架解体引起神经元生长锥的塌陷。当将NIH 3 T3细胞接种到ephrinA 1包被的表面上时，细胞既粘附又扩散。粘附和扩散伴随着肌动蛋白和微管细胞骨架的变化进行。EphA 2、粘着斑激酶（FAK）和p130（cas）被鉴定为在肝配蛋白诱导的形态学变化中的主要肝配蛋白依赖性磷酸酪氨酸蛋白。来自FAK（-/-）和p130（cas-/-）小鼠的小鼠胚胎成纤维细胞（MEFs）在ephrinA 1诱导的细胞扩散中存在严重缺陷，分别在FAK或p130 cas重新表达后逆转。组成型活性EphA 2的表达诱导NIH 3 T3细胞经历相同的，但配体独立的形态学变化。这些数据表明，ephrinA 1可以诱导细胞粘附和肌动蛋白细胞骨架的变化，在成纤维细胞中的FAK和p130（cas）依赖性的方式，通过激活EphA 2受体。这一发现，肝配蛋白Eph信号可以导致肌动蛋白细胞骨架组装，而不是拆卸，有许多影响肝配蛋白Eph反应在其他类型的细胞。
Ephrins and Eph receptors are involved in axon guidance and cellular morphogenesis. An interaction between ephrin and Eph receptors elicits neuronal growth-cone collapse through cytoskeletal disassembly. When NIH3T3 cells were plated onto an ephrinA1-coated surface, the cells both adhered and spread. Adhesion and spreading proceeded concomitantly with changes in both the actin and microtubule cytoskeleton. EphA2, focal adhesion kinase (FAK) and p130(cas) were identified as the major ephrin-dependent phosphotyrosyl proteins during the ephrin-induced morphological changes. Mouse embryonic fibroblasts (MEFs) derived from FAK(-/-) and p130(cas-/-) mice had severe defects in ephrinA1-induced cell spreading, which were reversed after re-expression of FAK or p130 cas, respectively. Expression of a constitutively active EphA2 induced NIH3T3 cells to undergo identical, but ligand-independent, morphological changes. These data show that ephrinA1 can induce cell adhesion and actin cytoskeletal changes in fibroblasts in a FAK- and p130(cas)-dependent manner, through activation of the EphA2 receptor. The finding that ephrin-Eph signalling can result in actin cytoskeletal assembly, rather than disassembly, has many implications for ephrin-Eph responses in other cell types.