INVASION OF EPITHELIAL-CELLS BY SHIGELLA-FLEXNERI INDUCES TYROSINE PHOSPHORYLATION OF CORTACTIN BY A PP60(C-SRC)-MEDIATED SIGNALING PATHWAY
INVASION OF EPITHELIAL-CELLS BY SHIGELLA-FLEXNERI INDUCES TYROSINE PHOSPHORYLATION OF CORTACTIN BY A PP60(C-SRC)-MEDIATED SIGNALING PATHWAY
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DOI：
10.1002/j.1460-2075.1995.tb07244.x
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发表时间：
1995-06-01
期刊：
影响因子：
11.4
通讯作者：
SANSONETTI, PJ
中科院分区：
文献类型：
--
作者：
DEHIO, C;PREVOST, MC;SANSONETTI, PJ
福氏志贺菌通过侵袭结肠上皮细胞引起人类细菌性痢疾。细胞入侵是通过细菌定向吞噬作用发生的，这一过程需要在细菌进入部位聚合肌动蛋白。我们表明，福氏志贺氏菌入侵HeLa细胞诱导皮质蛋白酪氨酸磷酸化，皮质蛋白是一种宿主细胞蛋白，以前被认为是原癌蛋白pp60(c-src)的细胞骨架相关蛋白酪氨酸激酶(PTK)底物。免疫定位实验表明，Cortactin被募集到细菌进入过程中形成的膜下肌动蛋白细丝中，尤其是在细菌内化后早期吞噬细菌的进入结构的膜褶皱中，以及吞噬小体的外围，Cortactin高度浓缩。原癌蛋白pp60(c-src)似乎介导了皮质肌动蛋白的酪氨酸磷酸化，由于这种PTK在HeLa细胞中的过表达特异性地增加了细菌进入过程中诱导的皮质肌动蛋白酪氨酸磷酸化水平，在pp60(c-src)过表达的HeLa细胞中的免疫定位研究表明，pp60(c-src)被招募到进入结构和吞噬小体的外围，在那里pp60(c-src)似乎与膜结合积聚，我们的结果表明，福氏葡萄球菌对上皮细胞的入侵涉及pp60(c-src)的募集和激酶激活。原癌蛋白pp60(c-src)的信号传递可能在促进福氏志贺氏菌进入上皮细胞的细胞骨架变化中发挥作用，因为在HeLa细胞中瞬时过表达pp60(c-src)可以引起膜褶皱，似乎也刺激细菌对非侵袭性福氏志贺氏菌的摄取。
Shigella flexneri causes bacillary dysentery in humans by invading epithelial cells of the colon. Cell invasion occurs via bacterium-directed phagocytosis, a process requiring polymerization of actin at the site of bacterial entry, We show that invasion of HeLa cells by S.flexneri induces tyrosine phosphorylation of cortactin, a host cell protein previously identified as a cytoskeleton-associated protein tyrosine kinase (PTK) substrate for the proto-oncoprotein pp60(c-src). Immunolocalization experiments indicate that cortactin is recruited to submembranous actin filaments formed during bacterial entry, In particular, cortactin is highly enriched in membrane ruffles of the entry structure, which engulf entering bacteria, and also in the periphery of the phagosome early after bacterial internalization. The proto-oncoprotein pp60(c-src) appears to mediate tyrosine phosphorylation of cortactin, since overexpression of this PTK in HeLa cells specifically increases the level of cortactin tyrosine phosphorylation induced during bacterial entry, Immunolocalization studies in pp60(c-src)-overexpressing HeLa cells indicate that pp60(c-src) is, recruited to the entry structure and to the periphery of the phagosome, where pp60(c-src) appears to accumulate in association with the membrane, Our results suggest that epithelial cell invasion by S.flexneri involves recruitment and kinase activation of pp60(c-src). Signalling by the protooncoprotein pp60(c-src) may play a role in cytoskeletal changes that facilitate S.flexneri uptake into epithelial cells, since transient overexpression of pp60(c-src) in HeLa cells can provoke membrane ruffling and appears also to stimulate bacterial uptake of a non-invasive S.flexneri strain.