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PKG II inhibits EGF/EGFR-induced migration of gastric cancer cells.
- Source :
-
PloS one [PLoS One] 2013 Apr 16; Vol. 8 (4), pp. e61674. Date of Electronic Publication: 2013 Apr 16 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Background: Our previous research results showed that Type II cGMP dependent protein kinase (PKG II) could block the activation of epidermal growth factor receptor (EGFR) and consequently inhibit the proliferation and the related MAPK/ERK-mediated signal transduction of gastric cancer cell line BGC-823, suggesting that PKG II might inhibit other EGFR-triggered signal transduction pathways and related biological activities of gastric cancer cells. This paper was designed to investigate the potential inhibition of PKG II on EGF/EGFR-induced migration activity and the related signal transduction pathways.<br />Methodology/principal Findings: In gastric cancer cell line AGS, expression and activity of PKG II were increased by infecting the cells with adenoviral construct encoding PKG II cDNA (Ad-PKG II) and treating the cells with cGMP analogue 8-pCPT-cGMP. Phosphorylation of proteins was detected by Western Blotting and active small G protein Ras and Rac1 was measured by "Pull-down" method. Cell migration activity was detected with trans-well equipment. Binding between PKG II and EGFR was detected with Co-IP. The results showed EGF stimulated migration of AGS cell and the effect was related to PLCγ1 and ERK-mediated signal transduction pathways. PKG II inhibited EGF-induced migration activity and blocked EGF-initiated signal transduction of PLCγ1 and MAPK/ERK-mediated pathways through preventing EGF-induced Tyr 992 and Tyr 1068 phosphorylation of EGFR. PKG II bound with EGFR and caused threonine phosphorylation of it.<br />Conclusion/significance: Our results systemically confirms the inhibition of PKG II on EGF-induced migration and related signal transduction of PLCγ1 and MAPK/ERK-mediated pathways, indicating that PKG II has a fargoing inhibition on EGF/EGFR related signal transduction and biological activities of gastric cancer cells through phosphorylating EGFR and blocking the activation of it.
- Subjects :
- Cell Line
Cell Line, Tumor
Cell Movement genetics
Cyclic GMP analogs & derivatives
Cyclic GMP-Dependent Protein Kinase Type II genetics
ErbB Receptors genetics
Humans
Phosphorylation drug effects
Phosphorylation genetics
Signal Transduction drug effects
Signal Transduction genetics
Stomach Neoplasms genetics
Thionucleotides
Cell Movement drug effects
Cyclic GMP-Dependent Protein Kinase Type II metabolism
Epidermal Growth Factor pharmacology
ErbB Receptors metabolism
Stomach Neoplasms metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23613900
- Full Text :
- https://doi.org/10.1371/journal.pone.0061674