Type II cGMP-dependent protein kinase inhibits EGF-triggered signal             transduction of the MAPK/ERK-mediated pathway in gastric cancer cells.
Our previous study found that Type II cGMP-dependent protein kinase (PKG II)             is expressed at lower levels in human gastric cancer tissues and cell lines and             increasing the expression and activity of PKG II inhibited the proliferation of             cancer cell line BGC-823. However, the mechanism through which PKG II inhibits             proliferation of gastric cancer cells is still not clear. Herein, we show that             PKG II can inhibit EGF-induced MAPK signal transduction. In the gastric cancer             cell line BGC-823, the expression and activity of PKG II were increased by infecting             the cells with adenoviral construct encoding PKG II cDNA and treating the cells             with the cGMP analogue 8-pCPT-cGMP. We found that PKG II inhibited the EGF-induced             dual phosphorylation of ERK, a key component of the MAPK signal transduction pathway.             Upstream of ERK, PKG II inhibited the phosphorylation of MEK1/2, the phosphorylation/activation             of Raf-1, the activation of Ras, and the binding between adaptor protein Grb2             and GTP exchange factor Sos1 induced by EGF. Of note, PKG II inhibited the tyrosine             phosphorylation of EGFR induced by EGF. Downstream of ERK, the EGF-induced nuclear             translocation of phospho-ERK was also inhibited by PKG II. The results suggest             that PKG II inhibits the proliferation of gastric cancer cells through blocking             EGF-triggered MAPK signal transduction and the key blocking point is the tyrosine             phosphorylation of the EGF receptor.
School of Medical Science and Medical Technology, Jiangsu University, Zhenjiang, Jiangsu 212013, PR China.
Yan
Y
Wu
Yongchang
Y
Chen
Rui
R
Qu
Ting
T
Lan
Jianrong
J
Sang
D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051380:GRB2 Adaptor Protein / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D015689:Oncogene Protein p21(ras) / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D020837:SOS1 Protein / Q000378:metabolism; D013274:Stomach Neoplasms / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D051380:GRB2 Adaptor Protein; D020837:SOS1 Protein; D014443:Tyrosine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D019908:Proto-Oncogene Proteins c-raf; D017869:Cyclic GMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D015689:Oncogene Protein p21(ras); D013936:Thymidine