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 β (PDGFRβ) 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 PDGFRβ. 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 PDGFRβ and phosphorylated it, and thereby inhibited PDGF‐BB‐induced activation of PDGFRβ, and downstream PI3K/Akt and MAPK/ERK pathways. Mutation at Ser254 of PDGFRβ to alanine abolished the above inhibitory effects of secretory PKG II on PDGFRβ, indicating that Ser254 was the specific site phosphorylated by secretory PKG II. In conclusion, secretory PKG II inhibited PDGFRβ activation via Ser254 site.