Type II Cyclic Guanosine Monophosphate-dependent Protein Kinase Inhibits Epidermal Growth Factor Receptor Activation in Different Cancer Cell Lines

Overview

Journal Oncol Lett

Specialty Oncology

Date 2015 Jul 3

PMID 26137146

Citations 3

Authors

L U Jiang

Min Wu

Yan Wu

Ting Lan

Ying Wang

Hai Qian

Yongchang Chen

Affiliations

Soon will be listed here.

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.

Citing Articles

Cyclic Guanosine Monophosphate (cGMP)-Dependent Protein Kinase II Blocks Epidermal Growth Factor (EGF)/Epidermal Growth Factor Receptor (EGFR)-Induced Biological Effects on Osteosarcoma Cells.

Li D, Hua Y, Jiang L, Huang Y, Yue J, Wu Y Med Sci Monit. 2018; 24:1997-2002.

PMID: 29617357 PMC: 5900801. DOI: 10.12659/msm.905892.

The constitutively active PKG II mutant effectively inhibits gastric cancer development a blockade of EGF/EGFR-associated signalling cascades.

Wu Y, Yuan M, Su W, Zhu M, Yao X, Wang Y Ther Adv Med Oncol. 2018; 10:1758834017751635.

PMID: 29434677 PMC: 5802699. DOI: 10.1177/1758834017751635.

Protein Kinases Type II (PKG II) Combined with L-Arginine Significantly Ameliorated Xenograft Tumor Development: Is L-Arginine a Potential Alternative in PKG II Activation?.

Wu Y, Liu Y, Cai Z, Qin H, Li H, Su W Med Sci Monit. 2018; 24:736-742.

PMID: 29401205 PMC: 5810367. DOI: 10.12659/msm.906213.

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