Involvement of focal adhesion kinase in invasin-mediated uptake
Involvement of focal adhesion kinase in invasin-mediated uptake
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DOI：
10.1073/pnas.95.23.13658
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发表时间：
1998-11-10
影响因子：
11.1
通讯作者：
Isberg, RR
中科院分区：
文献类型：
--
作者：
Alrutz, MA;Isberg, RR
肠致病性假结核耶尔森氏菌（Yersinia pseudotuberculosis）高效进入非吞噬细胞是由细菌外膜蛋白侵袭素（invasin）介导的。侵袭素介导的摄取需要侵袭素与宿主真核细胞上的多个β 1链整联蛋白受体的高亲和力结合。以前使用抑制剂的研究表明，高效率的摄取需要酪氨酸激酶活性。在本文中，我们证明了一个要求粘着斑激酶（FAK）的侵袭素介导的摄取。显性干扰形式的FAK的过表达减少了细菌进入的量。具体而言，FAR的自磷酸化位点是细菌内化所需的，其是报道的c-Src激酶结合位点，因为缺乏自磷酸化位点的衍生物的过表达也具有显性干扰效应。表达Src激酶干扰变体的培养细胞也显示出减少的细菌摄取，证明Src家族激酶参与侵袭素促进的摄取。
High-efficiency entry of the enteropathogenic bacterium Yersinia pseudotuberculosis into nonphagocytic cells is mediated by the bacterial outer membrane protein invasin, Invasin-mediated uptake requires high affinity binding of invasin to multiple beta 1 chain integrin receptors on the host eukaryotic cell. Previous studies using inhibitors have indicated that high-efficiency uptake requires tyrosine kinase activity. In this paper we demonstrate a requirement for focal adhesion kinase (FAK) for invasin-mediated uptake. Overexpression of a dominant interfering form of FAK reduced the amount of bacterial entry. Specifically, the autophosphorylation site of FAR, which is a reported site of c-Src kinase binding, is required for bacterial internalization, as overexpression of a derivative lacking the autophosphorylation site had a dominant interfering effect as well. Cultured cells expressing interfering variants of Src kinase also showed reduced bacterial uptake, demonstrating the involvement of a Src-family kinase in invasin-promoted uptake.