Secretory type II cGMP-dependent protein kinase blocks activation of PDGFRβ via Ser254 in gastric cancer cells

The study of secretory protein kinase is an emergent research field in recent years. The secretion phenomenon of type II cGMP-dependent protein kinase (PKG II) was found in our latest research and our previous study confirmed that PKG II inhibited platelet-derived growth factor receptor beta (PDGFR beta) activation induced by platelet-derived growth factor BB (PDGF-BB) within the gastric cancer cells. Thus, this study was designed to investigated effect of secretory PKG II on PDGFR beta. Transwell assay and CCK8 assay indicated that secretory PKG II reversed PDGF-BB-induced cell migration, invasion, and proliferation. Immunoprecipitation, GST pull down and Western blotting results showed that secretory PKG II combined with extracellular domains of PDGFR beta and phosphorylated it, and thereby inhibited PDGF-BB-induced activation of PDGFR beta, and downstream PI3K/Akt and MAPK/ERK pathways. Mutation at Ser254 of PDGFR beta to alanine abolished the above inhibitory effects of secretory PKG II on PDGFR beta, indicating that Ser254 was the specific site phosphorylated by secretory PKG II. In conclusion, secretory PKG II inhibited PDGFR beta activation via Ser254 site.