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PKG II inhibits PDGF‐BB triggered biological activities by phosphorylating PDGFRβ in gastric cancer cells
Author(s) -
Wang Ying,
AppiahKubi Kwaku,
Lan Ting,
Wu Min,
Pang Ji,
Qian Hai,
Tao Yan,
Jiang Lu,
Wu Yan,
Chen Yongchang
Publication year - 2018
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.11020
Subject(s) - platelet derived growth factor receptor , phosphorylation , protein kinase b , signal transduction , receptor tyrosine kinase , mapk/erk pathway , tyrosine phosphorylation , microbiology and biotechnology , chemistry , cancer research , kinase , biology , receptor , growth factor , biochemistry
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 PDGFRβ 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 PDGFRβ and phosphorylated this receptor, and thereby inhibited PDGF‐BB induced activation of PDGFRβ, 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 PDGFRβ activation but mutation of Ser643 had no such an effect, indicating that Ser712 was PKG II‐specific phosphorylating site of PDGFRβ. In conclusion, PKG II inhibited PDGFRβ activation in gastric cancer via phosphorylating Ser712 of this RTK.

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