Trypanosoma cruzi Targets Akt in Host Cells as an Intracellular Antiapoptotic Strategy
Trypanosoma cruzi Targets Akt in Host Cells as an Intracellular Antiapoptotic Strategy
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DOI：
10.1126/scisignal.2000374
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发表时间：
2009-11-17
影响因子：
7.3
通讯作者：
PereiraPerrin, Mercio
中科院分区：
文献类型：
--
作者：
Chuenkova, Marina V.;PereiraPerrin, Mercio
引起南美锥虫病的寄生虫克氏锥虫在其宿主细胞的胞质溶胶中分化，然后复制和传播感染，这些过程需要受感染细胞的长期存活。在这里，我们表明，在细胞质中，寄生虫源性神经营养因子（PDNF），一种位于T。cruzi是丝氨酸-苏氨酸激酶Akt（一种抗凋亡分子）的底物和激活剂。PDNF增加编码Akt的基因的表达，同时抑制编码促凋亡因子的基因的转录。因此，PDNF激发持续的功能反应，保护宿主细胞免受氧化应激和促炎细胞因子肿瘤坏死因子-α和转化生长因子-β诱导的凋亡。考虑到PDNF还通过与神经营养表面受体TrkA结合来激活Akt，我们提出这种蛋白质通过充当受体结合配体来激活细胞表面的存活信号，并且通过充当受体下游的支架衔接蛋白来激活细胞内部的存活信号。
The parasite Trypanosoma cruzi, which causes Chagas' disease, differentiates in the cytosol of its host cell and then replicates and spreads infection, processes that require the long-term survival of the infected cells. Here, we show that in the cytosol, parasite-derived neurotrophic factor (PDNF), a trans-sialidase that is located on the surface of T. cruzi, is both a substrate and an activator of the serine-threonine kinase Akt, an antiapoptotic molecule. PDNF increases the expression of the gene that encodes Akt while suppressing the transcription of genes that encode proapoptotic factors. Consequently, PDNF elicits a sustained functional response that protects host cells from apoptosis induced by oxidative stress and the proinflammatory cytokines tumor necrosis factor-alpha and transforming growth factor-beta. Given that PDNF also activates Akt by binding to the neurotrophic surface receptor TrkA, we propose that this protein activates survival signaling both at the cell surface, by acting as a receptor-binding ligand, and inside cells, by acting as a scaffolding adaptor protein downstream of the receptor.