PKG II inhibits PDGF-BB triggered biological activities by phosphorylating PDGFRß in gastric cancer cells.
Cell Biol Int
; 42(10): 1358-1369, 2018 Sep.
Article
em En
| MEDLINE
| ID: mdl-29935031
ABSTRACT
Previous studies revealed that type II cGMP-dependent protein kinase G (PKG II) could inhibit the activation of epidermal growth factor receptor (EGFR) which is a widely investigated RTK. PDGFR belongs to family of receptor tyrosine kinases (RTKs) too. However, the effect of PKG II on PDGFR activation is not clear yet. This study investigated potential regulatory effect of PKG II on activation of PDGFRß and the downstream signaling transductions in gastric cancer. The results from CCK8 assay and Transwell assay indicated that PDGF-BB induced cell proliferation and migration. Activated PKG II reversed the above variations caused by PDGF-BB. Immunoprecipitation and Western blotting results showed that PKG II combined with PDGFRß and phosphorylated this receptor, and thereby inhibited PDGF-BB induced activation of PDGFRß, and MAPK/ERK and PI3K/Akt mediated signal transduction pathways. Based on the prediction by phosphorylation site software, Ser643 and Ser712 were mutated to alanine respectively which prevented phosphorylation at these sites. Mutation at Ser712 abolished the inhibitory function of PKG II on PDGFRß activation but mutation of Ser643 had no such an effect, indicating that Ser712 was PKG II-specific phosphorylating site of PDGFRß. In conclusion, PKG II inhibited PDGFRß activation in gastric cancer via phosphorylating Ser712 of this RTK.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptor beta de Fator de Crescimento Derivado de Plaquetas
/
Proteína Quinase Dependente de GMP Cíclico Tipo II
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cell Biol Int
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China