Src is required for cell migration and shape changes induced by fibroblast growth factor 1
Src is required for cell migration and shape changes induced by fibroblast growth factor 1
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DOI：
10.1038/sj.onc.1203050
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发表时间：
1999-11-18
期刊：
影响因子：
8
通讯作者：
Zhan, X
中科院分区：
文献类型：
--
作者：
Liu, JL;Huang, C;Zhan, X
成纤维细胞生长因子1（FGF-1）是一种有效的趋化因子，可诱导皮质肌动蛋白相关蛋白（coronin）的酪氨酸磷酸化。FGF-1诱导的coronin的酪氨酸磷酸化需要酪氨酸残基421、482和466，这些残基是蛋白酪氨酸激酶Src体外靶向的。此外，FGF-1不能诱导来源于Src敲除小鼠（Src（-/-））的细胞内的皮质素的酪氨酸磷酸化，表明Src是FGF-1诱导的皮质素的酪氨酸磷酸化所必需的。虽然Src-/-细胞能够经历快速增殖，但它们对FGF-1的形状改变和细胞迁移的响应受损。形态学分析进一步揭示，FGF-1不能诱导极化板状伪足的形成和corneum易位到Src（-/-）细胞的前缘。与对FGF-1的促有丝分裂反应一致，Src的缺乏不影响Snt（或Frs 2）的酪氨酸磷酸化，Snt（或Frs 2）是连接至Ras的FGF-1早期信号蛋白。因此，我们的数据支持Src和corneum参与FGF信号通路的概念，所述FGF信号通路用于细胞迁移和形状改变而不是有丝分裂。
Fibroblast growth factor 1 (FGF-1) is a potent chemotactic factor and induces tyrosine phosphorylation of a cortical actin-associated protein (cortactin). The tyrosine phosphorylation of cortactin induced by FGF-1 requires the tyrosine residues 421, 482 and 466, which are targeted by the protein tyrosine kinase Src irt vitro. Furthermore, FGF-1 is unable to induce tyrosine phosphorylation of cortactin within the cells derived from Src knockout mice (Src(-/-)), indicating that Src is required for the tyrosine phosphorylation of cortactin induced by FGF-1. Although Src-/- cells are able to undergo rapid proliferation, they are impaired to respond to FGF-1 for the shape change and cell migration. Morphological analysis further reveals that FGF-1 fails to induce the formation of polarized lamellipodia and the translocation of cortactin into the leading edge of Src(-/-) cells. Consistent with the mitogenic response to FGF-1, the lack of Src does not affect the tyrosine phosphorylation of Snt (or Frs2), a FGF-1 early signaling protein that links to Ras, Therefore, our data support the notion that Src and cortactin participate in a FGF signal pathway for cell migration and shape change rather than mitogenesis.