Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1.
Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1.
复制标题
DOI：
10.1083/jcb.200909095
复制
发表时间：
2010-07-12
期刊：
影响因子：
--
通讯作者：
Meyer TF
中科院分区：
文献类型：
--
作者：
Mehlitz A;Banhart S;Mäurer AP;Kaushansky A;Gordus AG;Zielecki J;Macbeath G;Meyer TF
衣原体编码的蛋白Tarp在宿主细胞质中被磷酸化，是抗凋亡信号分子的多价中心。许多细菌病原体将效应蛋白易位到宿主细胞中以操纵宿主细胞功能。在这里，我们使用的蛋白质微阵列，包括几乎所有的人类SRC同源2（SH2）和磷酸酪氨酸结合域，全面和定量评估宿主细胞蛋白和早期沙眼衣原体效应蛋白易位肌动蛋白募集磷蛋白（Tarp），这是迅速酪氨酸磷酸化的宿主细胞进入之间的相互作用。我们发现了许多新的人类SH2结构域和磷酸肽来自Tarp之间的相互作用。衔接蛋白SHC1是Tarp最强的相互作用伙伴之一。感染过程中SHC1依赖性基因调控的转录组分析表明，SHC1调节凋亡和生长相关基因。SHC1敲低使受感染的宿主细胞对肿瘤坏死因子诱导的凋亡敏感。总的来说，我们的研究结果揭示了SHC1在早期C。沙眼诱导的细胞存活，并建议Tarp功能作为一个多价磷酸化依赖的信号枢纽，这是重要的衣原体感染的早期阶段。
The Chlamydia-encoded protein Tarp is phosphorylated in the host cell cytoplasm and is a multivalent hub for antiapoptotic signaling molecules. Many bacterial pathogens translocate effector proteins into host cells to manipulate host cell functions. Here, we used a protein microarray comprising virtually all human SRC homology 2 (SH2) and phosphotyrosine binding domains to comprehensively and quantitatively assess interactions between host cell proteins and the early phase Chlamydia trachomatis effector protein translocated actin-recruiting phosphoprotein (Tarp), which is rapidly tyrosine phosphorylated upon host cell entry. We discovered numerous novel interactions between human SH2 domains and phosphopeptides derived from Tarp. The adaptor protein SHC1 was among Tarp’s strongest interaction partners. Transcriptome analysis of SHC1-dependent gene regulation during infection indicated that SHC1 regulates apoptosis- and growth-related genes. SHC1 knockdown sensitized infected host cells to tumor necrosis factor–induced apoptosis. Collectively, our findings reveal a critical role for SHC1 in early C. trachomatis–induced cell survival and suggest that Tarp functions as a multivalent phosphorylation-dependent signaling hub that is important during the early phase of chlamydial infection.
登录
查看更多内容
DOI：
10.1073/pnas.0603044103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Jewett, Travis J.;Fischer, Elizabeth R.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
影响因子：
3.1
作者：
Buchholz, Kerry R.;Stephens, Richard S.
通讯作者：
Stephens, Richard S.
DOI：
10.1016/j.bbrc.2008.04.089
发表时间：
2008-06-27
影响因子：
3.1
作者：
Jewett, Travis J.;Dooley, Cheryl A.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
影响因子：
4.8
作者：
Chen, XM;Splinter, PL;LaRusso, NF
通讯作者：
LaRusso, NF
影响因子：
5.3
作者：
Juban, Gaetan;Giraud, Guillaume;Morle, Francois
通讯作者：
Morle, Francois