PKG II inhibits EGF/EGFR-induced migration of gastric cancer cells.
PKG II inhibits EGF/EGFR-induced migration of gastric cancer cells.
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PKG II 抑制 EGF/EGFR 诱导的胃癌细胞迁移
DOI：
10.1371/journal.pone.0061674
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Gu L
中科院分区：
文献类型：
--
作者：
Jiang L;Lan T;Chen Y;Sang J;Li Y;Wu M;Tao Y;Wang Y;Qian H;Gu L
背景本课题组前期研究发现，Ⅱ型cGMP依赖性蛋白激酶（PKG II）可阻断表皮生长因子受体（EGFR）的激活，从而抑制胃癌细胞BGC-823的增殖及MAPK/ERK介导的相关信号转导，提示PKG II可能抑制EGFR触发的胃癌细胞的其他信号转导途径及相关生物学活性。本论文旨在研究PKG Ⅱ对EGF/EGFR诱导的细胞迁移活性的抑制作用及其相关信号转导途径。方法/主要发现在胃癌细胞系AGS中，通过用编码PKG II cDNA的腺病毒构建体（Ad-PKG II）感染细胞并用cGMP类似物8-pCPT-cGMP处理细胞，PKG II的表达和活性增加。Western Blotting检测蛋白质磷酸化水平，“Pull-down”法检测活性小G蛋白Ras和Rac 1。用trans-well设备检测细胞迁移活性。用Co-IP检测PKG II和EGFR之间的结合。结果表明EGF促进AGS细胞迁移，其作用与PLCγ1和ERK介导的信号转导通路有关。PKG II通过抑制EGF诱导的EGFR的Tyr 992和Tyr 1068磷酸化，抑制EGF诱导的细胞迁移活性，阻断EGF启动的PLCγ1和MAPK/ERK信号转导通路。结论PKG Ⅱ能抑制EGF诱导的胃癌细胞迁移及PLCγ1和MAPK/ERK介导的相关信号转导，提示PKG Ⅱ通过磷酸化EGFR并阻断其活化，对EGF/EGFR相关信号转导和胃癌细胞生物学活性具有深远的抑制作用。
Background Our previous research results showed that Type II cGMP dependent protein kinase (PKG II) could block the activation of epidermal growth factor receptor (EGFR) and consequently inhibit the proliferation and the related MAPK/ERK-mediated signal transduction of gastric cancer cell line BGC-823, suggesting that PKG II might inhibit other EGFR-triggered signal transduction pathways and related biological activities of gastric cancer cells. This paper was designed to investigate the potential inhibition of PKG II on EGF/EGFR-induced migration activity and the related signal transduction pathways. Methodology/Principal Findings In gastric cancer cell line AGS, expression and activity of PKG II were increased by infecting the cells with adenoviral construct encoding PKG II cDNA (Ad-PKG II) and treating the cells with cGMP analogue 8-pCPT-cGMP. Phosphorylation of proteins was detected by Western Blotting and active small G protein Ras and Rac1 was measured by “Pull-down” method. Cell migration activity was detected with trans-well equipment. Binding between PKG II and EGFR was detected with Co-IP. The results showed EGF stimulated migration of AGS cell and the effect was related to PLCγ1 and ERK-mediated signal transduction pathways. PKG II inhibited EGF-induced migration activity and blocked EGF-initiated signal transduction of PLCγ1 and MAPK/ERK-mediated pathways through preventing EGF-induced Tyr 992 and Tyr 1068 phosphorylation of EGFR. PKG II bound with EGFR and caused threonine phosphorylation of it. Conclusion/Significance Our results systemically confirms the inhibition of PKG II on EGF-induced migration and related signal transduction of PLCγ1 and MAPK/ERK-mediated pathways, indicating that PKG II has a fargoing inhibition on EGF/EGFR related signal transduction and biological activities of gastric cancer cells through phosphorylating EGFR and blocking the activation of it.
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影响因子：
37.3
作者：
Hu T;Li C
通讯作者：
Li C
影响因子：
7.3
作者：
Rangaswami H;Schwappacher R;Marathe N;Zhuang S;Casteel DE;Haas B;Chen Y;Pfeifer A;Kato H;Shattil S;Boss GR;Pilz RB
通讯作者：
Pilz RB
DOI：
10.1006/bbrc.1996.0477
发表时间：
1996-03-27
影响因子：
3.1
作者：
Orstavik, S;Solberg, R;Sandberg, M
通讯作者：
Sandberg, M
影响因子：
--
作者：
THEROUX, SJ;STANLEY, K;DAVIS, RJ
通讯作者：
DAVIS, RJ
GEP100/Arf6 是人肝癌 HepG2 细胞中表皮生长因子诱导的 ERK/Rac1 信号传导和细胞迁移所必需的
影响因子：
3.7
作者：
Hu Z;Du J;Yang L;Zhu Y;Yang Y;Zheng D;Someya A;Gu L;Lu X
通讯作者：
Lu X