Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seodaemunku Shinchondong 134, Seoul 120-752, Korea.
J Biol Chem. 2010 May 21;285(21):16042-50. doi: 10.1074/jbc.M110.111054. Epub 2010 Mar 26.
The Helicobacter pylori protein CagA may undergo tyrosine phosphorylation following its entry into human gastric epithelial cells with downstream effects on signal transduction. Disruption of the gp130 receptor that modulates the balance of the SHP2/ERK and JAK/STAT pathways enhanced peptic ulceration and gastric cancer in gp130 knock-out mice. In this study, we evaluated the effect of translocated CagA in relation to its tyrosine phosphorylation status on the gp130-mediated signal switch between the SHP2/ERK and JAK/STAT3 pathways. We showed that in the presence of CagA, SHP2 was recruited to gp130. Phosphorylated CagA showed enhanced SHP2 binding activity and ERK1/2 phosphorylation, whereas unphosphorylated CagA showed preferential STAT3 activation. These findings indicate that the phosphorylation status of CagA affects the signal switch between the SHP2/ERK and JAK/STAT3 pathways through gp130, providing a novel mechanism to explain H. pylori signaling.
幽门螺杆菌蛋白 CagA 在进入人胃上皮细胞后可能发生酪氨酸磷酸化，从而对信号转导产生下游影响。破坏调节 SHP2/ERK 和 JAK/STAT 途径平衡的 gp130 受体，会增强 gp130 敲除小鼠的消化性溃疡和胃癌。在这项研究中，我们评估了转位 CagA 与其酪氨酸磷酸化状态对 gp130 介导的 SHP2/ERK 和 JAK/STAT3 途径之间信号转换的影响。我们表明，在存在 CagA 的情况下，SHP2 被募集到 gp130 上。磷酸化的 CagA 显示出增强的 SHP2 结合活性和 ERK1/2 磷酸化，而未磷酸化的 CagA 则优先激活 STAT3。这些发现表明，CagA 的磷酸化状态通过 gp130 影响 SHP2/ERK 和 JAK/STAT3 途径之间的信号转换，为解释幽门螺杆菌信号提供了一种新的机制。
