title: PKG II reverses HGF-triggered cellular activities by phosphorylating serine 985 of c-Met in gastric cancer cells.
abstract: Previous studies showed that type II cGMP-dependent protein kinase G (PKG II) could inhibit the activation of epidermal growth factor receptor (EGFR). Both c-Met and EGFR belong to family of receptor tyrosine kinases (RTKs) and have high molecular analogy. However, the effect of PKG II on c-Met activation is unclear. This study was designed to investigate the inhibitory effect of PKG II on the activation of c-Met and consequent biological activities. The results from CCK8 assay, Transwell assay and TUNEL assay showed that HGF enhanced cell proliferation and migration, and decreased cell apoptosis. Activated PKG II reversed the above changes caused by HGF. Immunoprecipitation and Western blotting results showed that PKG II could bind with c-Met and phosphorylate its Ser985, and thereby inhibited HGF-induced activation of c-Met and MAPK/ERK and PI3K/Akt/mTOR mediated signal transduction. When Ser985 of c-Met was mutated to Alanine for preventing phosphorylation of this site, the blocking effect of PKG II on c-Met activation was annulled. When Ser985 of c-Met was mutated to Aspartic acid for mimicking phosphorylation of this site, HGF-induced activation of c-Met was prevented. In conclusion, the results indicated that PKG II could block c-Met activation via phosphorylating Ser985 of this RTK.
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Basic Medical Department, Changchun Medical College, Changchun City, Jilin Province, PR China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Miaolin
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Ting
authors.initials: T
authors.lastname: Lan
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Pang
authors.affiliation: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang City, Jiangsu Province, PR China.
authors.forename: Yongchang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D045744:Cell Line, Tumor; D062967:Cyclic GMP-Dependent Protein Kinase Type II / Q000378:metabolism*; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: C066855:HGF protein, human; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D062967:Cyclic GMP-Dependent Protein Kinase Type II; C569729:PRKG2 protein, human
keywords: c-Met; gastric cancer cell; inhibition; phosphorylation; type II cGMP-dependent protein kinase G