title: Type II cyclic guanosine monophosphate-dependent protein kinase inhibits epidermal growth factor receptor activation in different cancer cell lines.
abstract: Previous data has revealed that type II cyclic guanosine monophosphate-dependent protein kinase (PKG II) inhibits epidermal growth factor (EGF)-induced phosphorylation/activation of the epidermal growth factor receptor (EGFR) and mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) in gastric cancer cells. The aim of the present study was to determine whether PKG II inhibited EGF-induced phosphorylation/activation of EGFR and MAPK/ERK in cell lines derived from different cancer tissues. SW480, HepG2, OS-RC-2, A549, MCF-7 and U251 cells were transfected with adenoviral constructs encoding PKG II cDNA (Ad-PKG II) to upregulate the expression of PKG II, and then treated with 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP) in order to activate the kinase. Western blot analysis was performed to investigate the phosphorylation of EGFR and MAPK/ERK. The results demonstrated that treatment with 100 ng/ml EGF for 5 min increased the tyrosine (Tyr)1068 phosphorylation of EGFR and the threonine 202/Tyr204 phosphorylation of MAPK/ERK. Transfecting the cells with Ad-PKG II, and stimulating the kinases with 8-pCPT-cGMP efficiently inhibited the EGF-induced phosphorylation of EGFR and MAPK/ERK. The results revealed that PKG II had an inhibitory effect upon EGFR activation and the consequent MAPK/ERK-mediated signaling of cell lines derived from the various cancer tissues.
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: L U
authors.initials: LU
authors.lastname: Jiang
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lan
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chen
keywords: cancer cells; epidermal growth factor; inhibition; receptor; type II cyclic guanosine monophosphate-dependent protein kinase