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.