Grb2 is a key mediator of Helicobacter pylori CagA protein activities
Grb2 is a key mediator of Helicobacter pylori CagA protein activities
复制标题
DOI：
10.1016/s1097-2765(02)00681-0
复制
发表时间：
2002-10-01
期刊：
影响因子：
16
通讯作者：
Sasakawa, C
中科院分区：
文献类型：
--
作者：
Mimuro, H;Suzuki, T;Sasakawa, C
幽门螺杆菌CagA进入胃上皮细胞后发生酪氨酸磷酸化并诱导宿主细胞形态学改变。在这里，我们表明，CagA可以在体外和体内与Grb 2相互作用，这导致Ras/MEK/ERK通路的激活，并导致细胞分散以及增殖。重要的是，CagA的这种能力与酪氨酸磷酸化无关，酪氨酸磷酸化发生在CagA的五个重复的EPIYA序列（PY区）内。然而，PY区似乎是必不可少的Grb 2结合和诱导的细胞反应。因此，细胞内CagA通过与Grb 2结合，可能作为一个传感器，刺激生长因子样下游信号，导致细胞形态变化和增殖，这是H.幽门诱导的胃增生
CagA delivered from Helicobacter pylori into gastric epithelial cells undergoes tyrosine phosphorylation and induces host cell morphological changes. Here we show that CagA can interact with Grb2 both in vitro and in vivo, which results in the activation of the Ras/MEK/ERK pathway and leads to cell scattering as well as proliferation. Importantly, this ability of CagA is independent from the tyrosine phosphorylation, which occurs within the five repeated EPIYA sequences (PY region) of CagA. However, the PY region appears to be indispensable for the Grb2 binding and induction of the cellular responses. Thus, intracellular CagA via its binding to Grb2 may act as a transducer for stimulating growth factor-like downstream signals which lead to cell morphological changes and proliferation, the causes of H. pylori-induced gastric hyperplasia.