title: Type II cGMP-dependent protein kinase inhibits ERK/JNK-mediated activation             of transcription factors in gastric cancer cells.
abstract: A previous study has shown that type II cGMP‑dependent protein kinase (PKG             II) inhibits the proliferation of gastric cancer cells through blocking EGF-triggered             MAPK/ERK signal transduction, indicating that the kinase may be a potential anticancer             factor. In the present study, the role of PKG II in the EGF-induced activation             of transcription factors in the MAPK/ERK signal transduction pathway was investigated.             BGC-823 human gastric cancer cells were infected with adenoviral constructs encoding             the cDNA of PKG II (pAd‑PKG II) to increase the expression of PKG II and treated             with 8-pCPT‑cGMP to activate the enzyme. Using luciferase reporter assays, it             was revealed that PKG II markedly suppressed the EGF-induced transcriptional activities             of AP-1 and Elk1. Consistent with the inhibitory effect of PKG II on AP-1 activity,             the expression levels of c-Jun and c-Fos, components of AP-1, were also inhibited.             Co-immunoprecipitation analysis demonstrated that EGF treatment increased the             AP-1 content through inducing the formation of p-c-Jun-c-Jun homodimers and p-c-Jun-c-Fos             heterodimers. However, this combination was efficiently blocked by activated PKG II.             While pretreatments with MAPK inhibitors suppressed the EGF-induced transcriptional             activities of AP-1 and Elk1, PKG II prevented the EGF-induced phosphorylation/activation             of ERK and JNK, but not the phosphorylation of p38MAPK induced by EGF. These data             suggest that PKG II inhibits the EGF-triggered proliferation of gastric cancer             cells through suppressing ERK-/JNK-, but not p38MAPK, -mediated AP-1 and Elk1             transactivation.
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Jiangsu 212013, PR China. sangjianrong@yahoo.com.cn
authors.forename: Jianrong
authors.initials: J
authors.lastname: Sang
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chen
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Yan
authors.initials: Y
authors.lastname: Tao
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yueying
authors.initials: Y
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Lan
authors.forename: Genbao
authors.initials: G
authors.lastname: Shao
mesh_terms: D045744:Cell Line, Tumor; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D050807:ets-Domain Protein Elk-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D004815:Epidermal Growth Factor; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases